Obesity in Childhood

Michael Rosenbaum and Rudolph L. Leibel

Pediatr. Rev. 1989;11;43-55
DOI: 10.1542/pir.11-2-43

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Obesity in Childhood
Michael Rosenbaum, MD,* and Rudolph L. Leibel, MDt

immediate and long-term conse-

The questions below should help quences.
EDUCATIONAL OBJECTIVE
focus the reading of this article.
1. What is the pathophysiologic sig- DIAGNOSTIC CRITERIA FOR 21. The pediatrician should have
nificance of fat cell hypertrophy and OBESITY IN CHILDREN knowledge to make an appropriate
hyperplasia? evaluation of a 4-year-old girl who
Obesity is a maladaptive increase
2. What is the role of environment is obese, differentiating among cx-
in the amount of energy stored as fat.
compared to heredity in determining ogenous obesity, central nervous
Optimal body fat stores for a given
obesity? system lesion (tumor, trauma, in-
individual depend upon factors such
fection), endocrinopathies (hypo-
3. Which endocrine causes of obesity as age, intercurrent health, genotype,
are associated with less than average thyroidism, hyperinsulinism, Cush-
and environment. It was probably not
height for age? ing syndrome, ingestion of exoge-
maladaptive, for example, for our dis-
nous steroids), and congenital
4. What happens to adolescents who tant progenitors to be generously en-
syndromes (Prader-Willi, Laur-
follow unsupervised weight reduction dowed with fat as a provision against
diets? ence-Moon-BiedI, Alstrom, Vas-
prolonged periods of starvation. Sim-
quez, X-chromosome, pseudohy-
ilarly, there are physiologic states,
poparathyroidism), and develop an
such as early pregnancy, when it may
appropriate plan for management
It is estimated that as many as 25% be advantageous to store more en-
(Topics, 89/90).
of children and 30% of adults in the ergy as fat.
United States are obese. Clinicians Ideally, any diagnostic test of obe-
need little reminding of the intractable sity should possess the following at-
nature of this disorder and the need tributes: (1) easily performed in an (muscle, liver, brain, bone, etc), and
for more effective and long-lasting outpatient setting, (2) not confounded other methods such as isotope dis-
therapies, Obesity in childhood may by other body mass covariates such tribution, are not practical as routine
lay the foundation of the degenerative as height, (3) yield reproducible re- screening devices in children. The
cardiovascular diseases that may or suIts that can be tracked and most accurate of the readily available
may not be grossly evident until adult- matched against available reference methods of assessing fat mass in
hood. Obese children manifest many standards, and (4) correlate with pre- children is the direct measure of sub-
of the same disturbances (eg, hyper- sent and/or future adiposity-related cutaneous fat mass at various ana-
insulism, hyperlipidemia, and hyper- morbidity. Unfortunately, no currently tomic sites using skinfold calipers.
tension) as obese adults. Tracking available technique meets all of these Skinfold thickness measurements are
studies of obesity, hypertension, and criteria. All current methods for defin- made by grasping the subcutaneous
serum lipid values from childhood to ing obesity in children rely on statis- tissue between the thumb and fore-
adulthood have indicated that these tical comparisons of given measure- finger approximately 6 to 8 cm apart,
variables track well, ie, that the ments to population norms rather shaking it gently to exclude underly-
obese, hypertensive, hyperlipidemic than an individualized functional as- ing muscle, and stretching it just
child is likely to remain obese, hyper- sessment of the risk of adiposity-re- enough to permit the jaws of a spring-
tensive, and hyperlipidemic through- lated morbidity and of the likelihood actuated skinfold caliper to compress
out many years. The observation that of persistence of obesity into adult- the tissue. This procedure should not
hyperlipidemia, obesity, and other hood. This actuarial approach is produce any pinching or discomfort
factors associated with an increased reasonable at present because we do to the subject; the mean value of
risk of subsequent cardiovascular not yet possess the means to make three to five repeat measurements
disease that are noted in childhood prognostications that take account of should be used. Skinfold thickness
tend to persist into adulthood empha- specific genetic or environmental measurements may not be as repro-
sizes the importance of screening in variables on an individual basis. ducible as various mathematical per-
selected children to identify those at These points should be borne in mind mutations of weight for height ratios
risk for subsequent morbidity. Pedia- when considering the diagnosis of (in particular, body mass index [BMI]
tricians should recognize obesity as obesity in an individual child. = weight [kg]/height [mJ2), and some
a significant disease entity with both The various methods of assessing practice is required to become profi-
fat mass, and the extent to which cient in the use of skinfold calipers.
each meets these idealized criteria, On the positive side, normative data
* Research Associate, The Laboratory of Hu- are summarized in Table 1. Densi- for skinfold thicknesses are readily
man Behavior and Metabolism, The Rockefeiler tometry (the comparison of weight in available (Fig 1) and, unlike absolute
University, New York. air to that submerged in water), which weight or BMI, skinfold measure-
t Associate Professor, Laboratory of Human has long been regarded as the gold ments give some indication of body
Behavior and Metabolism, Rockefeller Univer-
sity. Dr Leibel is an Established Investigator of standard for assessing adipose tis- fat distribution and will not mislabel
the American Heart Association. sue mass relative to lean body mass muscular children as obese. An in-

pediatrics in review #{149} vol. 11 no. 2 august 1989 PIR 43

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Obesity

4C
TABLE 1. Characteristics of Different Means of Body Composition FEMALES
-4--
Assessrnent* 35
0
Conven- Reproduc- Standards Independent Assesses MOrbidity -I 30
Method Available of Height Distribution Correlated 0
ence ibility U.
25
Weight 4+ 4+ 4+ + + 2+ (I)
Body mass index 4+ 4+ 4+ 3+ + 2+ 20
-J
Skinfolds 3+ 3+ 4+ 4+ 3+ 3+
a. 15
Densitometry + 3+ 3+ 4+ + 3+ 4
3
Isotopic + 3+ 2+ 4+ + 3+ 10

Total body electri- 2+ 3+ 4+ + ?

(05
cal conductivity
Nuclear magnetic 2+ 3+ 2+ 4+ 4+ 4+
resonance, 0
roentgenogram,

*
etc.
Results range
which indicates
from + which indicates that method
method fully meets criteria.
poorly meets idealized criteria to 4+
EE35
4

: :
MALES
I 1 I 1-
-

25 . #{149}.... 95th

creasing body of evidence suggests oral glucose tolerance test vary di-
that the distribution of fat may be rectly with subscapular skinfold thick-
more predictive of an individuals risk ness and other indices of truncal adi-
of adiposity-related morbidity than posity in children and adults. The ob-
their overall degree of fatness. The servation that subscapular skinfold
predominantly abdominal distribution thickness correlates highly with both 2 4 6 8 10 12 14 16 18 20

of adipose tissue (android pattern, morbidity (blood pressure and cho- AGE IN YEARS
abdominal/gluteal circumference ra- lesterol) and the degree of truncal fat
tio > 0.90 in adult women, >1 .0 in distribution further emphasizes the Fig 1. Smoothed percentiles of subscapular
importance of assessing fat distribu- skinfold thicknesses for children aged 2 to 18
tion as well as relative fatness of the years. Children with measures >75%ile for age
entire body. Skinfold thickness meas- and sex should be considered at risk for
The distribution of body fat adiposity-related morbidity (reprinted with per-
urement, especially at the subscapu- mission from Johnson CL, FulwoodR, Abraham
may be as, or more, lar skinfold, should be included in the 5, et al. Basic data on anthropometric meas-
important than absolute routine evaluation of the growing urements and angular measurements of the hip
fatness in determining the child and should definitely be per- and knee joints for selected age groups 1-74
risk of obesity-related formed in the child who is obese to years of age. Vital Health Stat. 1981 ;1 1:1-9).
morbidity in both children Method of skinfold thickness measurement is
visual inspection. reviewed in Cameron N. The methods of aux-
and adults. ological anthropometry. In: Falkner F, Tanner
MORBIDITIES OF PEDIATRIC JM, eds. Human Growth. New York, NY:
Plenum Press; 1 978;2:35-90.
OBESITY
adult men) is associated with a higher
risk of stroke, diabetes, ischemic been noted in children because of
Psychologic Morbidities
heart disease, and overall mortality self-imposed caloric restriction aris-
than the gynecoid (pelvic) pattern (ab- Obese children are subjected to ing from fears of becoming obese.
dominal/gluteal circumference ratio < considerable psychologic stress. There are few objective studies of
0.75 in women, < 0.85 in men) of fat Many members of modern western the psychologic consequences of pe-
distribution. The association with societies view obesity as a conse- diatric obesity. Some investigators
myocardial infarction is independent quence of self-indulgence and over- have reported that body image dis-
of age, BMI, serum cholesterol and gratification. The obese child is gen- turbances, characterized by feelings
triglycerides, and systolic blood pres- erally portrayed in the media as an of depression, of loathsomeness, and
sure. The reasons for this association unattractive, clumsy, glutton. Con- of being viewed contemptuously by
are not clear but may reflect the ef- versely, these same societies laud others, are significantly more fre-
fects of intraabdominal fat depots on extreme thinness as an ideal. As early quent in obese than nonobese ado-
hepatic metabolism. It has been sug- as kindergarten, children asked to lescents. Although obese preadoles-
gested, for example, that large ab- rate potential playmates based on cents showed evidence of these psy-
dominal depots may increase am- questions and photographs chose a chiatric disturbances, the symptoms
bient free fatty acid concentrations in playmate with a major visible physical were less severe than in those sub-
the liver, resulting in diminished insu- handicap over one who was obese. jects who had become obese as ad-
lin breakdown and enhanced triglyc- The negative images associated with olescents or in those whose preado-
ende synthesis. Blood pressure and obesity are so strong that growth lescent obesity persisted into adoles-
serum insulin levels during a standard failure and delayed puberty have cence. Other investigators have not

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in review #{149} vol. 1 1 no. 2 august
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 NUTRITION

found any differences in ratings of malize with weight reduction. At the associated with increased ACTH re-
self-esteem or body image between level of the hypothalamic-pituitary lease. ACTH will also stimulate in-
obese or lean children. Pediatricians axis, obese children and adults have creased production of adrenal sex
should avoid jumping to the immedi- diminished prolactin release in re- steroids such as dehydroepiandros-
ate conclusion that a child is neces- sponse to provocative stimuli and di- terone (OHEA) and testosterone.
sarily severely depressed because of minished basal and stimulated This physiologically appropriate in-
obesity or that every obese child is growth hormone release. Somato- crease in ACTH release may account
strongly motivated to lose weight. medin production and growth are, if for the elevated serum concentra-
anything, increased in the obese child tions of adrenal sex steroids and
and the lack of growth hormone re- early adrenarche commonly noted in
Medical Morbidities
lease reverses rapidly with weight obese children. Circulating concen-
Obesity adversely affects many or- loss. The normal or increased growth trations of gonadal sex steroids are
gan systems in adults and children. and somatomedin production are also abnormal in obese children.
The relative risk of hypertension most likely due, at least in part, to the Obese adolescents tend to have an
among obese adults (BMI > 27.8 for hyperinsulinism associated with obe- earlier pubarche than their lean age-
men, 27.3 for women vs normal sity. Adrenal glucocorticoid and sex matched peers. Assessment of go-
values of 21 .5 for men and 23.3 for steroid production is increased in nadal function is complicated by an
women) aged 20 to 45 years is five obese children. Obese children main- adiposity-related decrease in circulat-
to six times that of their nonobese tain normal serum cortisol levels, de- ing concentrations of sex hormone-
counterparts. In the same age group, spite an increase in urinary excretion binding globulin which results in a
the risks of diabetes and of hypercho- of glucocorticoid metabolites (1 7-hy- higher fraction of serum sex steroids
lesterolemia (>250 mg/dL fasting) droxy steroids). These observations which are unbound, and therefore
are increased 2.9 and 1 .5 times, re- suggest that cortisol clearance, like bioactive, than in lean individuals.
spectively, in obese individuals. Sim- creatinine clearance, is increased in This may yield artifactually low total
ilarly, mortality ratios are significantly obese individuals in direct proportion serum sex steroid concentrations.
higher among overweight men and to an increase in lean body mass. Obese adolescent boys appear to
women (defined as 40% more than Because cortisol is the major regula- have a diminished testicular response
average weight for age and sex) for tor of pituitary ACTH release, the in- to human chorionic gonadotropin, al-
cardiovascular disease, stroke, can- creased cortisol clearance may be though this may be an artifact of de-
cer, and digestive disease.
Obesity represents the most corn-
mon identifiable cause of hyperten-
sion in children. Other risk factors for TABLE 2. Endocrine Function in Obese Children
cardiovascular disease, including hy- Endocrine
perlipidemia, elevated low-density Ii- Changes in Obese Individuals
System
poproteins, and decreased high-den-
Somatotroph Basal and stimulated growth hormone release following
sity lipoproteins, correlate positively hypothalamic or pituitary stimuli; normal cIrculating soma-
with excess adiposity. Thus, the tomedins and normal or accelerated statural growth
same risk factors for cardiovascular Lactotroph I Basal serum prolactin but release in response to provoc-
morbidity that are traditionally asso- ative stimuli
ciated with adult adiposity-related Gonadotroph Normal serum luteinizing hormone and follicle-stimulating
morbidity are also present in children. hormone
Pulmonary function tests reveal ven- Thyroid Normal basal serum thyroxine, normal or tniodothyroxine,
tilation/perfusion abnormalities that normal or thyroid-stimulating hormone; normal reverse
,

decrease arterial oxygenation. Ab- tniodothyroxine, normal or tniodothyroxine receptors in

normalities of respiratory muscle monocytes
Adrenal Normal serum cortisol with cortisol production and excre-
function and central respiratory reg- tion of cortisol metabolites; normal urinary free cortisol,
ulation can culminate in the pickwick- normal circadian rhythms, earlier adrenarche; serum ad-
ian syndrome in children or adults. renal androgens and DHEA, normal epinephnne and nor-
Overlapping skinfolds are common epinephrine.
sites for intertrigo and furunculosis in Testis Total serum testosterone with normal free testosterone
the obese child. Coxa vara, slipped due to sex hormone-binding
,, globulin, I serum estrogen
femoral epiphyses, Blount disease, but rarely with symptoms of hyperestorgenism; obese
and Legg-Calve-Perthe disease oc- boys tend to enter earlier pubarche than their lean peers
cur with highest frequency in the Ovary Normal serum estrogen, j, sex hormone binding globulin,
earlier pubarche than lean peers; I incidence of dysmen-
obese adolescent.
orrhea, dysfunctional uterine bleeding, polycystic ovarian
Although obese individuals dem-
syndrome
onstrate many endocrine abnormali- Endocrine I Insulin and glucagon release, resistance to insulin-me-
ties (Table 2), in virtually all instances, pancreas diated glucose transport; j, release of pancreatic polypep-
these changes are covariants of body tide
weight or caloric intake that will nor-

pediatrics in review #{149} vol. 11 no. 2 august 1989 PIR 45

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Obesity

creased sex hormone-binding globu- of limited food intake (Table 3). In has attained a fat cell number ex-
lin. Obese children tend to have mildly addition to its role as an energy ceeding that of a normal adult, he or
elevated serum concentrations of tn- buffer, fat acts as insulation, pro- she will always remain hyperplastic.
iodothyronine (T3), probably reflecting vides protection for underlying tis- It is possible that it is such hyperpla-
an increased peripheral synthesis sues, and functions as a storage de- sia of adipose tissue that contributes
from thyronine (T4). Hypeninsulinemia pot for various steroids as well as to the increased likelihood of the per-
and resistance to insulin-mediated actively participating in their metabo- sistence ofjuvenile-onset obesity into
glucose transport are well known lism (eg, the aromatization of andro- adulthood that occurs with age.
concomitants of obesity. Obesity is stenedione to estrone). Excess body
the most common cause of insulin fat may be stored by increasing adi-
DEVELOPMENT OF ADIPOSE
resistance in adults and children. pocyte size (hypertrophy) and/or adi- TISSUES
However, chemical diabetes second- pocyte number (hyperplasia). In
any to obesity is rare in children. Note milder forms of obesity, hypertrophy In the fetus, differentiated fat cells
that obese subjects are not propor- of fat cells is usually the only morpho- are first detectable at about 15
tionally resistant to insulin action on logic change noted. As the severity weeks gestation. Adipocyte size and
noncarbohydrate systems, such as of obesity increases, so does the like- number continue to increase through-
amino acid metabolism, activation of lihood of fat cell hyperplasia. Unlike out gestation and achieve maximal
the enzyme lipoprotein lipase, and fat cell lipid content, which is change- growth rates at about the 30th week.
inhibition oflipolysis in adipose tissue. able, it appears that, when an adipo- Normally, during the last trimester of
The hypeninsulinemia of obesity may cyte has been formed, it cannot be pregnancy, fetal body fat content in-
thus favor the maintenance of the lost. Reduced-obese subjects who creases from 3% to 5% to approxi-
obese state by stimulating lipogene- have maintained a normal body mately 1 2% to 1 5% of body mass at
sis via activation of lipoprotein lipase weight for many years still have at birth. During the first year of life, per-
and by inhibiting lipolysis. The mech- least as many fat cells as they did centage of body fat increases to ap-
anisms of adiposity-related insulin re- when they were obese, even though proximately 25% in boys and 26% in
sistance involve receptor and post- that number may be three times that girls. After 1 year of age, there is a
receptor modifications, the exact na- of their lean peers. Hirsch and Batch- steady decline in percentage of body
tune of which remains largely un- elor noted that there was little differ- fat (to a prepubertal nadir of about
known. Adiposity-related hyperinsu- ence in adipocyte volume between 13% in boys and 17% in girls) and an
linism is reversible with weight loss the moderately obese (170% to increasing discrepancy between boys
and correlates directly with adipocyte 240% of ideal body weight) and the and girls. Just before the pubertal
size in vitro. Almost all of these en- superobese (>240% ideal body growth spurt (approximately age 7 to
docninopathies are fully reversible weight) and suggested that in man 9 years in boys and 6 to 8 years in
with weight loss and can be mimicked there may be a maximal adipocyte girls), the relative fat content of boys
by overfeeding lean subjects. It is lipid content of approximately 1 .0 g increases slightly to an average of
important for the clinician to bear in per cell. When this cell size is approximately 15%, whereas the per-
mind that these seeming endocrine reached, fat cell hypertrophy may act centage of body fat of girls increases
changes are generally not causal as a direct or indirect stimulus to to an average of 21 %. During adoles-
agents of obesity. Most causes of recruitment of new fat cells. cence, the percentage of body fat
secondary obesity, such as hypothy- Such a model raises important increases to approximately 17% to
roidism, are associated with impaired questions regarding the prognosis for 1 8% in boys and 27% to 28% in girls,
somatic growth, whereas obese chil- pediatric obesity that is detected at ie, young adult values (Fig 2). (Note
dren will generally be of average or different ages. If fat cell number is that these figures may be substan-
above average height, depending irreducible, then identification of the tially reduced in athletes and substan-
upon the age at which they are ex- child destined to become obese at as tially elevated in obese individuals.)
amined. Pediatricians evaluating the early an age as possible becomes Most adipose tissue growth during
obese child for abnormal pubarche or even more desirable. When a child the first 6 months of extrauterine life
adrenarche should note that these
events tend to normally occur earlier
in obese children because of the
growth-promoting effects of obesity TABLE 3. Energy Storage in 70-Kilogram Man*
and/or the effects of obesity on sex Fuel Tissue g kcal
steroid metabolism. Triglyceride Adipose 15000 105 000
Glycogen Liver 70 280
BASIC PHYSIOLOGY OF THE Muscle 120 480
DEVELOPMENT AND Glucose Body fluids 20 80
Protein Muscle 6000 25000
REGULATION OF BODY FAT
CONTENT *Reprinted with permission from Leibel RL, Berry EM, Hirsch J. Biochemistry
and Development of Adipose Tissue in Man. In: Conn HL Jr, DeFelice EA, Kuo
The major function of fat is to store P. Health and Obesity. New York, NY: Raven Press; 1983.
energy and to release it during times

PIR 46 pediatrics in review #{149} vol. 11 no. 2 august 1989

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Fig 2. Changes in body composition
FE Sex differences in fat patterning
adolescence, and young adulthood
in adolescence. In: Falkner F, Tanner JM, eds. Human Growth.
1 988;2:239-272. 0, giris and women; , boys and men.
appears to be via fat cell enlargement
rather than hyperplasia. After 2 years
of age, there is little further increase
in adipocyte size in the nonobese
child. It is generally agreed, however,
that fat cell number continues to in-
crease slowly until a peripubertal adi-
pose growth spurt occurs. Knittle and
his associates examined adipose tis-
sue biopsies from 178 nonobese and
110 obese children. They found that
there was no significant change in fat
cell size from ages 2 to 14 years and
no significant increase in fat cell num-
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NUTRITION
sized that menarche is somehow
triggered by the acquisition of a cer-
tam body composition (at least 17%
fat) and that continued menstruation
requires the maintenance of approxi-
mately 22% of body weight as fat.
This theory is consistent with the ob-
servation that obese girls tend to
have an earlier menarche, whereas
those with anorexia nervosa or ex-
treme thinness often become amen-
orrheic. It is possible that the aroma-
tization of androgens to estrogens by
adipose tissue results in the priming
the hypothalamic-pituitary axis to mi-
tiate normal cyclic gonadotropin (lu-
teinizing hormone and follicle-stimu-
lating hormone release. However, the
precise physiology of the relationship
between fatness and menstruation
has yet to be elucidated.
Although the mature adipocyte is
incapable of mitosis, there appear to
be a pool of cells (preadipocytes)
that can differentiate into adipocytes
under the appropriate conditions.
Such cells may be indistinguishable
from mesenchymal cell types unless
stimulated to complete differentia-
tion. Several investigators have pro-
posed that preadipocytes arise from
penicytes of the capillary endothe-
hum. Given the seemingly limited po-
tential for adipocyte hypertrophy,
some authors have also speculated
that, in vivo, a signal generated by
hypertrophied adipocytes may induce
the further differentiation of preadi-
pocytes. The induction of new adi-
pocytes would serve to reduce the
lipid content per cell, with a corre-
during childhood (reprinted with permission from Johnston sponding reduction in the adipocyte
in children and youth. Curr Top Nutr Dis. 1 988;1 7:85-102), induction signal.
(reprinted with permission from Forbes GB. Body composition
New York, NY: Plenum Press;
ENERGY HOMEOSTASIS
Obesity is ultimately the result of
ber from ages 2 to 10 years in non- an excess of energy intake (diet) rel-
obese subjects. However, in obese ative to energy expenditure. In this
subjects, there was continual adipo- sense, excessive adiposity is a reflec-
cyte hyperplasia at a time when adi- tion of the activities of systems con-
pocyte number was relatively stable trolling energy homeostasis rather
in nonobese persons. These data are than a primary abnormality of fat. If
consistent with the concept that the energy intake and utilization were en-
achievement of a critical adipocyte tirely independent processes, then
volume triggers adipocyte hyperpla- the prediction of change in body fat
sia. in response to dietary manipulation
A number of interesting theories or change in energy expenditure
have been offered regarding interac- would be comparatively simple. Any
tions between adipose tissue growth change in either of these parameters
and pubertal events. Fnisch hypothe- would result in a corresponding
pediatrics in review #{149} vol. 11 no. 2 august 1989 PIR 47
 Obesity

weight change of approximately 1

gram of fat per 7 kcal of alteration in TABLE 4. Regulation of Feeding
intake relative to expenditure. By tak-
Lateral
ing in 150 calories (a 240-mL [8-fl oz] Effects in Animals
Hypothalmus
Ventromedial Hypothalmus
glass of milk) more or less per day
than energy output, a persons body On feeding and me-
weight would then change by 21 .4 g/ tabolism
Hypothalamic stim- Hunger and Satiety and glycogenolysis
d or 7.8 kg/y. However, energy in- ulation glycogen
take, metabolic efficiency (calories synthesis
stored per calories consumed), and Hypothalamic de- Hypophagia Hyperphagia, hypersensitivity to
body mass are interrelated variables struction pleasant and unpleasant food
whose interlocking control mecha- dues, hypermnsulinemia
nisms are poorly understood. On hypothalamic
Feeding behavior in animals is reg- electrical activity
ulated by a complex set of internal Food cues or None
and external cues that inform the Cholecystokinin None I
organism when to initiate feeding, Neurotensin None I
Galanin None j,
what volume and/or calories to con- Neuropeptide y None j,
sume, and when to stop feeding. a-Adrenergic input None
Classically, investigators of central 3-Adrenergic input None
nervous system mechanisms regulat- Serotonin None
ing feeding behavior have viewed the Dopamine None
brain as having discrete hunger and Opiod None
satiety centers, located, respec-
tively, in the lateral hypothalamus and
ventromedial hypothalamus. Signal 0.3 kg of lean body mass (predomi-
output from these regions is influ- TABLE 5. Regulation of Feeding nantly muscle) per kilogram of weight
enced by various neurotransmitters, gained in adipose tissue. In other
circulating metabolites, and hon- Agents Increasing FoodIntake words, the excess weight of an
mones. Because other brain regions Nonmetabolizable glucose analogs
obese person is approximately 70%
Insulin
(eg, the paraventnicular nucleus and Androgens
to 75% fat and 20% to 25% lean
hindbrain), as well as widely distrib- Glucocorticoids body mass. Similarly, weight reduc-
uted fiber tracts, also influence feed- Barbiturates tion entails loss of both fat and lean
ing behavior, these hypothalamic 5-Hydroxytryptophan antagonists body mass.
areas are more accurately viewed as Norepinephnne and epinephnne Energy expenditure consists of vol-
components of central hunger and (a-effects) untary and obligatory components.
satiety systems that regulate feed- Opiate agonists Physical activity accounts for only
ing behavior via an interplay of central Neuroleptics about 10% of total energy utilization
Neuropeptide Y
and peripheral pathways (Tables 4 in the average adult. Although dimin-
and 5). Clonidine ished exercise capacity may accom-
Although adipose tissue repre- Agents Decreasing Food Intake pany obesity, lack of physical exer-
sents a significant proportion of body Glucose and glycerol cise does not necessarily result in
mass (as much as 70% in an obese Insulin obesity. A significant number of cal-
person as compared with 15% to Estrogens ones are probably expended in such
30% in the average nonobese adult), Prostaglandins activities as pacing, fidgeting, etc.
it uses relatively little energy (approx- Cholecystokinin However, there are few reliable stud-
Amphetamines
imately 3% of total resting energy ies quantifying differences in such ac-
5-Hydroxytryptophan
expenditure in an obese adult). The Norepinephnne and epinephnne tivities between lean and obese sub-
main reason for the low rate of energy (fl-effects) jects. Theoretically, even a small dif-
expenditure per unit mass of adipose Naloxone ference in average daily caloric
tissue is that 90% to 95% of the mass Serotonin expenditure would, throughout time,
of an adipocyte is accounted for by Atropine cause significant alterations in body
the inert, stored fat droplet. Lean Somatostatin mass if caloric intake were held con-
body mass is composed of all energy- Glucagon stant.
consuming tissues (mainly brain, Obligatory energy expenditure can
liver, kidney, and muscle), including be subdivided into metabolism which
the small fraction of adipocyte cellular requirements. Accordingly, caloric occurs in response to environmental
mass that consumes energy. Two intake and energy expenditure are stimuli (such as the work of digestion
persons of the same body mass, but better expressed per unit of energy- or maintenance of body temperature)
of different body composition, will dif- consuming tissue, ie, lean body and the resting metabolic rate which
fer substantially in resting energy mass. Adults and children gain about reflects primarily the work of cardiac

PIR 48 pediatrics in review #{149} vol. 1 1 no. 2 august 1989

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and respiratory muscles, of maintain-
ing tnansmembrane ion gradients,
and of protein turnover. In addition,
some investigators have suggested
that there is a third compartment to
systemic energy expenditure, consti-
tuted by metabolic fuel cycles that
consume adenosine tniphosphate
without performing useful biochemi-
cal work and, thereby, waste the
potential energy stored within the
chemical bonds of these substrates.
Examples include the simultaneous
processes of lipolysis and triglyceride
synthesis that occur in adipose tis-
sue, thermogenesis via the conver-
sion of the energy of stored triglyc-
enides directly into heat that occurs
in brown adipose tissue and glycolys-
isgluconeogenesis in liver. Although
the activation of such cycles (perhaps
by increased sympathetic nervous
system activity) may contribute to the
hypermetabolism encountered in Se-
vere stress states, such as burns,
their role in normal metabolic homeo-
stasis is, as yet, unclear. There has,
to date, been no demonstration of a
novel derangement of metabolic effi-
ciency that regularly causes obesity.
Studies in both human and animal
subjects have demonstrated that to-
tal energy expenditure declines more
quickly during periods of undernutri-
tion than would be predicted from
changes in caloric intake or lean body
mass. Leibel and Hirsch studied daily
weight maintenance energy require-
ments in 26 obese patients (mean
weight 1 52 8.4 kg) before and after
weight loss (mean reduced weight
100.2 5.7 kg). They found that
reduced obese subjects were able to
maintain their weight ingesting fewer
calories per day than lean control
subjects (mean weight 62.6 2.3
kg), even though they remained sig-
nificantly heavier. This maintenance
energy requirement in obese subjects
was 25% less than would be pre-
dicted on the basis of lean body mass
changes. The changes in energy use
observed during experimental altera-
tions of body weight suggest that
substrate is directed toward or away
from metabolic processes of varying
efficiency and/or cost depending on
body weight and nutrient supply. The
practical consequences of this are
that many formerly obese individuals
may have to reduce their caloric in-
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NUTRITION
take to levels significantly less than processes determines whether there
those of their never-obese lean peers is a net increase or depletion of lipid
to maintain weight reduction. Such a within the individual adipocyte, as
dietary regimen would require modi- well as total and regional intraadipo-
fication of many learned and/or ge- cyte lipid stores. The fundamental
netically programmed feeding behav- biochemical processes underlying Ii-
ions. Indeed, studies of energy ho- polysis and lipogenesis are schema-
meostasis following weight loss have tized in Fig 3. Since adipocytes are
suggested that the high rate of recid- sensitive to both 13i- (lipolytic) and a2
ivism among the obese may be due (antilipolytic)-adrenergic stimulation,
to an inability to reduce intake in pro- the relative degree of activation of
portion to the decrease in energy ex- these opposing systems can direct
penditure associated with weight cellular machinery toward fat storage
loss. or lipolysis.
The relative decrease in energy re- A number of points should be em-
quirements of the reduced-obese phasized regarding differences in adi-
person may affect the operation of pose tissue from different anatomic
various energy homeostatic mecha- regions and between children and
nisms acting to return such persons adults. Studies of fat cells have sug-
to a set point for adiposity which is gested that the growing child is more
higher in obese than in lean individ- sensitive to antilipolytic and lipogenic
uals. The persistence of a tendency stimuli than adults, ie, there is a
to gain weight, and the need to re- greater tendency for children to store
strict caloric intake even in the long- energy as fat. Studies of regional adi-
term reduced-obese person, sug- pose tissue have suggested that ab-
gests that the set point is not readily dominal fat is relatively more respon-
changeable. In this sense, obesity sive to /3i (lipolytic) stimuli than is
may represent a physiologic correc- gluteal fat. These differences may ac-
tion for a prior imbalance between count for the relative ease with which
energy intake and expenditure. The most adults lose abdominal com-
major systemic regulators of the rel- pared to gluteal fat, as well as sex-
ative activities of these cellular sys- related differences in fat distribution.
tems in man are tniiodothyronine and Another important regulator of Ii-
sympathetic nervous system activity. polysis and lipogenesis is insulin. In-
Peripheral conversion of thyroxine to sulin stimulates lipogenesis by induc-
triiodothyronine increases in re- ing lipoprotein lipase and enhancing
sponse to caloric excess and de- the uptake of glucose into the adi-
crease with weight loss (as in the pocyte and its conversion to glycer-
hypothyroidism commonly associ- ide-glycerol which can then serve as
ated with anorexia nervosa), resulting the backbone in de novo tniglycer-
in increased energy expenditure that ide synthesis. Insulin also diminishes
opposes weight gain and decreased lipolysis by inhibiting hormone-sensi-
energy expenditure opposing weight tive lipase. Obese persons do not
loss. Sympathoadrenal medullary demonstrate the same resistance to
status is determined by the release insulin-mediated antilipolysis as they
of epinephnine from the adrenal gland do to insulin-mediated glucose trans-
and local release of norepinephrine at port. Therefore the hyperinsulinism of
nerve terminals. Measurement of car- obesity may act to perpetuate the
diac sympathetic nervous system ac- obese state by inhibiting the break-
tivity in animals have suggested that down of stored triglycerides.
adrenergic tone varies directly with
body weight.
GENOTYPIC AND
Catecholamine-responsive pro-
ENVIRONMENTAL INFLUENCES
cesses may be major means by
ON ADIPOSITY
which body weight and energy ex-
penditure are regulated. In white adi- In man, obesity is clearly the result
pose tissue, triglycerides are simul- of interactions of potent environmen-
taneously synthesized (Iipogenesis) tal and genetic factors which are dif-
and broken down into their constitu- ficult to cleanly separate. The media
ent free fatty acids and glycerol (Ii- tends to portray the obese person as
polysis). The relative activity of these a slothful glutton and to suggest that
pediatrics in review #{149} vol. 11 no. 2 august 1989 PIR 49
Obesity

obesity is due to overeating and in- of obesity, the steady increase with
activity, ie, to environmental influ- age in the likelihood that the obese
ences. Numerous pre- and postnatal child will become an obese adult is
environmental factors-including in- due to the impact of environmental
trauterine nutrition, socioeconomic factors on feeding behaviors of the
status, education, geographic loca- child as the child becomes more in-
tion, family size, and, of course, dependent and is less restricted by
diet-have been correlated with sub- parental prohibitions against eating
sequent risk of obesity. In 1 968, Knit- calorically dense food. In a predomi-
tIe and Hirsch reported that over- or nantly genetic model of obesity, the
underfeeding of preweanling rat pups apparent increase with age of the
correlated with respective increases correlation between pediatric and
or decreases in body fatness in adult- adult fatness might reflect progres-
hood. Later demonstration that ex- sively greater phenotypic expression
treme obesity in man is due to hyper- of genetically programmed patterns
plasia of fat cells, and of the irreduc- of feeding behavior and/or metabolic
ible nature of fat cell number, efficiency as the child becomes more
suggested that feeding in certain cnit- autonomous in determining the fre-
ical periods of childhood might exert quency and quantity of food inges-
strong influences on subsequent fat- tion. The steadily increasing preva-
ness. However, genotype also exerts lence of obesity among children and
strong influences on body composi- adults in western countries suggests
Fig 3. Activation of lipogenesis and lipolysis.
tion and body habitus. The identifi- that the environment is becoming
Enzyme ilpoprotein ilpase (LPL) hydrolyzes tn- cation of certain genetic forms of no- more permissive to the expression of
glycerides which are constituents of lipopro- dent obesity, such as the fa/fa rat or genetic tendencies toward obesity
teins to free fatty acids (FFA) and glycerol the ob/ob mouse, in which obesity is which may have been advantageous
(molar ratio FFA to glycerol = 3: 1). FFA can
inherited as a simple mendelian re- to our ancestors in a more hostile
then be returned to circulation or transported
into adipocyte to be esterified and stored as cessive trait, has prompted a resurg- environment. Such earlier environ-
triglyceride. Insulin stimulates almost every ence of interest in genotypic influ- mental pressure(s) may have led to
step in the process of lipogenesis. Lipolysis ences on obesity and, hopefully, the preferential selection of a thrifty
depends upon activation of adenylate cyclase- helped to dispel the view that obesity
dependent metabolic cascade which culmi-
nates in phosphorylation (activation) of intra-
is purely the result of sloth and self-
cellular hormone-sensitive lipase (HSL). HSL indulgence. In none of these rodent
Obesity in children reflects
hydrolyzes triglycerides to FFA and glycerol. models has the specific metabolic le-
interaction of genetic
Certain molecules favor or inhibit lipolysis by sion predisposing them to obesity
increasing or decreasing activity of adenylate proclivity with permissive
been identified. Body composition
cyclase. Such stimulation or inhibition occurs environment.
via binding of specific molecules to adipocyte studies of twins reared apart and
membrane receptors. Activated receptor corn- studies comparing body composition
plex then binds to membrane stimulatory (Ns of adopted children with their biologic genotype which now, when starva-
or Gs) or inhibitory (Ni or Gi) proteins. Ns
vs their adoptive parents suggest tion is rarely a problem and western
protein stimulates adenylate cyclase and
thereby activates lipolytic cascade. Ni protein strong genetic influences on body life-style is increasingly sedentary, fa-
inhibits adenylate cyclase and thus decreases composition and fat distribution.
cilitates the achievement of the obese
rate of lipolysis. Norepinephrine and epineph-
rifle are mixed agonists and simultaneously phenotype.
activate both $i (lipolytic) and a2 (antilipolytic)
receptors. Thus, net effect of these molecules
The likelihood of persistence EFFECTS OF PRE- AND
on lipolysis is dictated by relative preponder- POSTNATAL NUTRITION
ance of 131and a2 receptors and their coupling of obesity into adulthood
(N or G) proteins. Adenosine is released by increases with age. A good model for the possible ef-
adipocytes (as a product of adenine nucleotide
metabolism) into periceilular space and prob-
fects ofprenatal overnutrition on sub-
ably acts as a tonic inhibitor of lipolysis. Mech- sequent adiposity is the infant of the
anism(s) by which the signal generated by The likelihood that a given degree gestationally diabetic mother. Gesta-
insulin-receptor interactions is transduced of body fatness and distribution of tional diabetes mellitus exposes the
within cells is unknown. Insulin inhibits lipol ysis nondiabetic fetus to high concentra-
adipose tissue will persist into adult-
by increasing activity of phosphodiesterase
(PDE) which dephosphorylates HSL. Process hood increases steadily with age and tions of circulating glucose which re-
does not appear to be mediated by effects on is dependent of the duration of obe- sult in fetal hypeninsulinism and in-
adenylate cyclase. , Insulin effect; cAMP, sity. The obese adolescent who has creased lipogenesis. Although the
cyclic adenosine monophosphate. (Reprinted been overweight for 2 years is still obese macrosomic infant of the dia-
with permission from Rosenbaum M, LeibelRL.
Pathophysiology of childhood obesity, in
more likely to become an obese adult betic mother has been well de-
Barnes LA et al, eds. Advances in Pediatrics. than the obese 10-year-old child who scribed, it is not clear that exposure
Boca Raton, FL: Year Book Medical Publish- has been overweight for 8 years. In a of the fetus to the milieu of the dia-
ers; 1988;35:73-1 37.) predominantly environmental model betic mother actually constitutes an

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 NUTRITION

independent risk factor for subse- maker reported an association be- have suggested that there are ge-
quent obesity. It is equally possible tween the amount of time spent netic influences on sucking patterns
that the increased frequency of adult watching television and obesity in and sensitivity to sweetened formu-
obesity in these formerly prenatally children. However, it is unclear las. Thus, the relative amount of car-
overnourished infants is due to the whether the children are obese be- bohydrate, fat, protein, or even the
phenotypic manifestation of a genetic cause they watch television or flavoring of an infant formula might
tendency toward obesity that was wnether they watch more television encourage an infant to eat more or
also evident in their diabetic, and because of social stimatization by less depending upon a persons
often obese, mothers. their peers because they are obese. food preference genotype.
The effects of prenatal undernutni-
tion in man on subsequent obesity GENOTYPIC INFLUENCES CAUSES OF SECONDARY
have been studied primarily through OBESITY
retrospective examinations of popu- Efforts to quantify the contribution
There are a number of neurologic
lations exposed to prolonged periods of genotype to body habitus have lesions, endocrinopathies, and syn-
consisted largely of the comparisons
of starvation as a result of man-made dromes that result in abnormalities
on natural disasters. In one study of of mono -and dizygotic twins who of systems regulating feeding behav-
presumably share a similar environ-
19-year-old men who were conceived ion and/or energy expenditure. Al-
ment and comparisons of body habi-
during the Nazi-imposed Dutch fa- though it is important for the clinician
mine of 1944 to 1945 (winter hun- tus between adopted children and to be aware of these causes of sec-
their natural vs their adoptive par-
ger), Ravelli et al noted that offspring ondary obesity, it should also be ne-
ents. Studies of twins have sug- membered that they are compara-
of women who were undernourished
during the first two trimesters of gested that as much as 80% of the tively rare and that most pediatric
pregnancy tended to be fatter as variance in skinfold thicknesses or obesity is not due to an identifiable
weight for height may be attributable
adults than controls from nonnutri- lesion. Children with primary obe-
to genotype. Studies of adoptees as
tionally deprived areas. Offspring of sity tend to undergo earlier puberty
women who were undernourished adults and as children have found
than their lean peers. The obese pre-
during the third trimester of preg- significant correlations of body mass adolescent tends to be of average on
nancy and early infancy tended to be index between female, but not male,
above-average stature before the on-
leaner as adults than controls. He adoptees and their biologic, but not set of puberty compared with his on
suggested that early fetal undernutn- adoptive, parents. Results of similar her nonobese classmates. In con-
tion may influence the activity of studies have revealed significant, but trast, and with the notable exception
less pronounced, genetic influences
hypothalamic systems regulating of hypeninsulinemia, most causes of
on body fat distribution. Approxi-
feeding and energy homeostasis, secondary obesity (eg, hypothyroid-
whereas later prenatal undernutrition mately 20% to 25% of the variance ism, hypercortisolism, hypothalamic
in the relative proportion of truncal vs
may influence intra- and extrauterine dysfunction, and growth hormone de-
peripheral fat may be attributable to ficiency) are associated with poor sta-
adipose tissue development. How-
ever, the between-group differences genotype. This genetic expression tural growth. Skeletal maturation
may be increased in times of over-
are small in a large study population, (bone age) and the presence on ab-
feeding, ie, there is a strong heritable
and it is not clear whether these data sence of age-appropriate secondary
reflect changes in body fat content or component to locations at which new
sexual characteristics provide valua-
in lean body mass. fat is accumulated in times of nutrient
ble clues that may quickly rule out
excess that may not be fully ex- causes of secondary obesity and
Studies of postnatal environmental
pressed unless the person overeats.
influences on fatness have only re- avoid extensive unnecessary testing.
emphasized the view that each child Studies of infant energy expenditure Obesity is present in a variety of
have suggested that infants of over-
has highly individualized energy re- rare congenital syndromes such as
weight mothers tend to have reduced
quirements and patterns of energy Prader-Labhart-WilIi, Alstrom, Laur-
homeostasis. Although formula-fed ence-Moon-Bandet-BiedI, and pseu-
infants tend to be longer and heavier dohypoparathynoidism. The associ-
than those who are breast-fed, there ated features of these syndromes are
is no evidence that formula-fed in- Most obesity in children does summarized in Table 6. The cause of
fants remain fatter than their breast- not have a primary endocrine the obesity in these syndromes ap-
fed peers later in life. Other environ- etiology. Virtually all pears to involve structural and/or
mental variables have also been im- endocrine changes seen in functional hypothalamic defects in-
plicated in the pathogenesis of obe- obesity are secondary and volving feeding behavior and insulin
sity. In the United States, obesity is reversible. release, although the exact patho-
more prevalent in children raised in physiologic mechanisms are not fully
urban communities and in smaller known.
families and also varies between dif- energy expenditure, ie, to have a The endocninopathies that may
ferent geographic regions, ethnic greater tendency to store fat than contribute to pediatric obesity follow
groups, and socioeconomic classes, their peers born to lean mothers. logically from an understanding of
according to Garn. Dietz and Gort- Studies of infant-feeding behavior systems regulating energy expendi-

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Obesity

TABLE 6. Causes of Secondary Obesity

Structural or
Syndrome l..es clinical Features

Prader-Labhart-Willi Deletion on chromosome 1 5q11.15 Short stature with small hands and feet, mental re-
tardation and neonatal hypotonia, cryptorchidism,
almond-shaped eyes and fish-mouth
AistrOm Unknown Childhood blindness due to retinal degeneration,
nerve deafness, acanthosis nigncans, chronic
nephropathy, primary hypogonadism in males
only, insulin-resistant diabetes, infantile obesity
(which may diminish in adulthood)
Laurence-Moon-Bardet-BiedI Unknown Retinitis pigmentosa and mental retardation, poly-
dactyly, central (hypothalamic) hypogonadism,
rarely glucose intolerance, deafness, or renal dis-
ease
Carpenter Unknown Mental retardation and acrocephaly, polydactyly
and/or syndact1y, male hypogonadism
Cohen Unknown Microcephaly and mental retardation, short stature,
dysmorphic fades
Acquired hypothalamic lesions Infectious (sarcoid, tuberculosis, Adipocyte hypertrophy with little hyperplasia, head-
arachnoiditis, encephalitis), vas- ache and visual disturbance, hyperphagia and hy-
cular malformations, neo- podipsia, hypersomnolence, convulsions, finicki-
plasms, trauma ness, central hypogonadism, hypothyroidism,
hypoadrenalism, central (vagal) hypennsulinism
and diabetes insipidus. hyperprolactinemia and ga-
Iactorrhea, type IV hypetlipidemia
Blounts Unknown Bowed legs and thial torsion
Cushings Hypercortisolism (primary or sec- Moon fades, central obesity (with lean body
ondary) mass), poor statural growth glucose intolerance
Hypothyroidism Central thyrotropin-releasing Hypometabolic state (constipation, hypotension,
hormone or thyroid-stimulating bradycardia, cold intolerance) cretinism (if congeni-
hormone or thyroidal (1 thyroid- tal)
stimulating hormone, usually
autoimmune)
Pseudo-hypoparathyroidism Familial (? X-linked), resistance to Short stature, short metacarpals and metatarsals,
(type I) parathyroid hormone short thick neck and round fades, mental retarda-
tion, subcutaneous calcifications, nsk other en-
docrinopathies (hypothyroidism, hypogonadism)
Primary hyperinsulinism Neisidioblastosis, Beckwith-Wie- Symptoms of hypoglycemia, neonatal hemihypertro-
demann syndrome, Insulinsoma phy (Beckwith-Wiedemann syndrome), intolerance
of fasting

tune. Hypothyroidism, whether hy- as Kallman syndrome or as a feature child with progressive obesity and/or
pothalamic, pituitary, on thyroidal, re- of craniopharyngioma) is associated hyperphagia, normal or excessive
suIts in an overall decline in energy with an increased deposition of fat in growth, and symptoms attributable
expenditure. The child with hypothy- a eunuchoid pattern (pelvic, abdomi- to hypoglycemia.
roidism may have excessive weight nal, and pectoral regions) and should
gain and poor statural growth, as well be considered in the child with pro- PREVENTION AND TREATMENT
as the more classic features of such gressive obesity, poor growth, and
OF PEDIATRIC OBESITY
as cold intolerance, hypotension, pubertal delay.
constipation, and lethargy. In children Primary hyperinsulinism may result Given the knowledge that the prey-
with hypercortisolism (Cushing syn- from an insulin-secreting pancreatic alence of obesity in the United States
drome), distinctive pattern of central tumor, hypersecretion of insulin by is steadily increasing and that this is
obesity, moon facies, and striae are pancreatic fi cells (neisidioblastosis), due, at least in part, to an environ-
apparent. Unlike persons with pri- and/or hypothalamic lesions. Regard- ment that promotes high food intake
mary obesity, who gain approxi- less of the etiology, hypeninsulinemic and low activity levels, it should the-
mately 0.45 kg (1 Ib) of lean body patients are in a chronic anabolic oretically be possible for the pediatri-
mass for every 1.35 kg (3 Ib) of fat, state and must consume excessive cian to modify the childs environment
cushingoid patients tend to grow quantities of food to avoid becoming in a way that will diminish the likeli-
poorly and to lose lean body mass as profoundly hypoglycemic. Children hood of the phenotypic expression of
their disease progresses. There are with hyperinsulinism may grow at any genetic proclivity for obesity.
also some subtler endocninopathies slow, normal, or accelerated rates Practically, the most that the average
in which obesity and poor growth and are extremely intolerant of any pediatrician can do to identify the
may be the initial complaint. Hypo- prolonged period of fasting. This di- child at risk for becoming obese is to
gonadotropic hypogonadism (such agnosis should be considered in the look for signs of excessive weight

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 NUTRITION

gain relative to height. Plotting of mount to the patients and their fami- of age is two to three times more
growth data on height and weight lies, one must also consider the rigors likely to becomes an obese adult than
velocity charts, as well as on stand- of therapy and stigmatization of the his or hen lean peers. This relative risk
and curves of absolute height and child that may occur as a result of increases to greater than sixfold
weight, is particularly important in having their weight become the cen- among adolescent boys.) Therefore,
children with a family history of adi- ten of family attention. reduction in absolute weight, as op-
posity-nelated morbidity (diabetes, The more radical treatments some- posed to reduction in rate of weight
hypertension, hypercholesterolemia, times used for severely obese adults gain, should rarely, if ever, be at-
and myocardial infarction before 55 (jaw wiring, gastric stapling, jejuno- tempted in the obese infant.
years of age) or obesity. ileal bypass) are not recommended All diets should be designed to pro-
We currently lack sufficient knowl- for children. The consequences of vide sufficient quantities of carbohy-
edge to effectively prevent or treat even moderate caloric restriction may drate, fat (especially essential fatty
most instances of pediatric obesity. include an impairment of statural or acids), protein, minerals, and vitamins
Hager et al examined adipose tissue brain growth. Thus, if possible, diet to fully meet lean tissue growth re-
cellularity in obese prepubertal girls therapy should be directed toward quirements. Special diets consist-
during a 1 .5 to 1 .9-year therapeutic slowing rates of fat accretion until ing of drastically altered relative con-
trial of a 1 200-kcal/d diet and exen- body composition is normalized tents of carbohydrate, protein, on fat
cise plan. They found that, although rather than toward restricting energy may be dangerous and yield no better
the rate of fat accretion was signifi- to the point of weight loss. This is results than a limited intake of a well-
cantly diminished in these subjects particularly important when consid- balanced diet. No a priori judgments
during the period of study compared ering the potential risks of caloric re- can be made as to individual caloric
to their pre-thenapeutic trial rates, striction to the obese infant. The like- requirements. Some suggested diets
the increase in fat cell number during lihood of the persistence of obesity are given in Fig 4, but ultimately, the
the therapeutic period was still signif- into adulthood is significantly lower in adequacy of a given plan must be
icantly greater than in age-matched the obese infant compared with the judged on the compliance and per-
lean controls. These data imply that older obese child, and the risks of formance of the individual patient.
fat cell hyperplasia can be therapeu- poor statural and brain growth are Contrary to popular conceptions,
tically restrained but that the influ- greater. (The obese infant < 2 years the obese child is generally not phys-
ences of previous genotypic on envi-
ronmental factors that predisposed
:i;i; Breakfast Lunch Dinner Snack(s) Dietary
these subjects to obesity may persist Composition
despite therapeutic intervention. 1200 1/2 cup skim milk 1 cup skim milk 1/2 cup skim milk 1/2 cup 2 milk
1/2 cup orange juice turkey sandwich 2 on. broiled chicken unsweetened 5 meat
Long-term studies of weight-reduced 1 scrambled egg (2 os. turkey with 1/2 can green beans gelatin 2 vegetable
children have demonstrated that 80% 1 slice whole wheat toast mustard and lettuce 1 cm. baked potato 5 bread
3/4 cup unsweetened on whole wheat bread) tossed salad 2 rat
to 90% return to their previous weight cereal raw carrot sticks (lettuce and cucumber) 3 fruit
percentiles-rates of recidivism that 1 tsp. diet jelly 1 fresh apple 1 tsp. butter
1 tsp. butter 2 tsp. low calorie
are comparable to those observed in salad dressing
adults. 1/2 cup unsweetened
canned_peaches
There are clear medical and psy- 1500 1/2 cup skim milk 1 cup skim milk 1 cup sugar-free lemcnade 1/2 cup skim milk 2 milk
chosocial benefits to weight neduc- 1/2 cup orange juice roast beef sandwich 3 oz. broiled chicken 8 animal crackers 7 meat
1 scrambled egg (2 os. roast beef with 1/2 cup green beans 2 vegetable
tion for the obese person. However, I slice whole wheat toast mustard and lettuce 1 small baked potato and 7 bread
the pediatrician must also be alert to 3/4 cup unsweetened on rye bread) tossed salad 2 fat
cereal raw carrot sticks (lettuce and cucumber) 1/2 cup skim milk 3 fruit
morbidity that attends such efforts. 1 tsp. diet jelly 1 fresh apple 2 tsp. low-calorie 6 saltine crackers
The Food and Drug Administration 1 tsp. butter 1/2 cup unsweetened salad dressing 1 os. part skim
gelatin 1/2 cup unsweetened milk cheese
continues to report significant mor- canned_peaches

bidity associated with low energy 1800 1/2 cup skim milk 1 cup skim milk 1 cup sugar-free lemonade 1/2 cup skim milk 2 milk
1/2 cup orange juice tunafish sandwich 3 os broiled chicken 8 saltine crackers 8 meat
diets in adults and children. Mallick 1 scrambled egg (1/2 cup of water-packed tuna, 1/2 cup green beans 1 Tbs. peanut butter 2 vegetable
found that 80% of teenagers using 1 slice whole wheat toast 1 tsp. mayonnaise, 1 small baked potato 8 bread
3/4 cup unsweetened lettuce and tomato, tossed salad and 4 fat
unsupervised diets taken from popu- cereal on whole wheat bread) (lettuce and cucsmber) 4 fruit
Ian books or magazines suffered from 1 fresh apple 1 Tbs. oil and vinegar 1/2 cup apple juice
1 tsp. diet jelly 1/2 cup unsweetened salad dressing 1 os. part skim
hunger, weakness, headaches, fa- 1 tsp. butter gelatin 1 small roll milk cheese
tigue, nausea, constipation, nervous- raw carrot sticks 1/2 cup unsweetened 4 whole wheat
canned peaches crackers
ness, dizziness, poor concentration, 2000 1/2 cup skim milk 1 cup skim milk 1 cup sugar-free lemonade 1/2 cup skim milk 3 milk
altered menstrual function, and/or 1/2 banana roast beef sandwich 3 os. broiled chicken 1 os. part skim 8 meat
1 scrambled egg (2 on. roast beef with 1/2 cup #{231}eenbeans milk cheese on 1 slice 2 vegetable
fainting. Adverse reactions to thera- 1 English muffin mustard and lettuce 1 small baked potato whole wheat bread 10 bread
peutic dieting are as highly individu- 3/4 cup unsweetened on rye bread) tossed salad 3 fat
cereal raw carrot sticks (lettuce and cucumber) and 4 fruit
alized as therapeutic responses, and 1 tsp. diet jelly 1 fresh apple 2 tsp. low-calorie

subjects must be closely monitored 1 tsp. butter 8 animal crackers salad dressing
1/2 cup unsweetened
1/2 cup apple juice
1 The. peanut butter
during caloric restriction. Although canned peaches 4 whole wheat

the psychosocial consequences of crackers

childhood obesity may seem para- Fig 4. Sample diets and dietary compositions of 1200- to 2000-kcal/d diets.

pediatrics in review vol. 1 1 no. 2 august 1989 PIR 53

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Sponsored on November 8, 2009
Obesity

ically underactive compared with lean scribes aggressive weight reduction, calorically dense foods and to in-
peers. However, encouragement of it is important to ascertain that the crease physical activity.
exercise will allow the child to ingest individual patient really is morbidly When adiposity-related morbidity
more calories during the treatment obese. When one attempts to identify (medical or psychologic) is evident,
period. those persons who are at high risk more aggressive intervention is war-
Studies of compliance of obese for current on future adiposity-related ranted. The hypertensive on diabetic
children with dietary regimens have morbidity and to avoid overly aggres- child should attempt to alter body
emphasized the importance of a fam- sive treatment for those who are not composition in no more than 1 year
ily-oriented approach to therapy. Re- at such risk, it may be necessary to to the point that the morbidity is no
fusal to adhere to a weight-reduction perform more extensive screening for longer evident. The child who is ex-
plan may be the manifestation of metabolic morbidity than is currently peniencing severe depression or
other psychologic stresses. For ex- routine practice. other psychologic illness attributable
ample, Dietz reported that children of The obese infant should receive an to being overweight should also at-
married parents lose weight at higher abbreviated evaluation for morbidity tempt weight reduction, perhaps with
rates than those of divorced parents. including measurement of blood pres- adjunctive psychotherapy. The initial
When a weight-reduction plan has sure and thyroid hormones. Although therapeutic approach should involve
been recommended, conflicts fre- blood pressure measurement is more closely supervised diet and exercise
quently arise between the patient and difficult in infants than older children, plans. Some investigators have re-
nondieting family members regarding hypertension is an important conse- ported greater patient adherence to
the degree of dietary restriction and quence of obesity and a sufficient such treatments if they are adminis-
who is permitted to eat different reason for undertaking therapeutic tered in conjunction with a behavior
foods. Meals may become battles weight control. Obesity may be an modification program (according to
rather than times of cooperation and early manifestation of hypothyroid- Dietz). Because of the risks associ-
encouragement for the obese child. ism, unassociated with other classical ated with attempts at weight reduc-
Dietary restriction should never be stigmata of this endocninopathy. The tion in children, such a plan should
presented in a punitive fashion. If profound neurologic sequelae of early include the input of a dietician, as well
possible, the obese child and the en- hypothyroidism justify heightened at- as monitoring of school performance,
tire family should adhere to a diet tention to this possible, if unusual, and frequent physical examination by
similar in composition if not quantity. cause of obesity in infancy. the pediatrician. If the patient is una-
Involvement of the entire family Children whose subscapular skin- ble to lose weight, and morbidity per-
should help to minimize the feelings fold thickness is greater than the 75th sists, then placement of the child in a
of isolation in the obese child. percentile should be viewed as obese highly supervised environment, such
and a plan initiated for gradual weight as a weight-reduction summer camp,
reduction or for weight maintenance should be considered. Needless to
until the child grows into his or say, a child who returns from a
Treatment, when undertaken, weight. Although blood pressure weight-reduction camp must con-
should recognize the high monitoring should be performed rou- tinue a weight control regimen to
likelihood of the need for tinely in all children, this measure- avoid a return to the previous obese
lifelong attention to the ment is particularly important in the state. There is no documented role
problem. In some instances, obese child. In children whose sub- at present for pharmacotherapy in
particularly in obese infants, scapular skinfold thickness exceeds pediatric obesity.
the risks of treatment- the 90th percentile for age, the risk Before beginning a controlled diet
induced morbidity may of immediate significant morbidity is and exercise plan, the obese child,
outweigh the potential great enough that within the context the pediatrician, and the family of the
benefits of treatment. of family history assessment of blood patient should recognize the difficul-
lipids and glucose tolerance should ties inherent in such a program. Stud-
be done. If adiposity-related morbid- ies of weight-reduced adolescents
When a therapeutic approach is ity is minimal or absent in such a child, and adults have demonstrated that
decided upon, children should be a weight-maintenance diet and exer- maintenance of a weight-reduced
classified with respect to apparent cise plan should be advised. The goal state may require ongoing restriction
morbidity. The presence of morbidity of such therapy is to allow the child of caloric intake to levels less than
that is potentially related to adiposity to grow normally so that he or she those anticipated solely on the basis
is an indication for more aggressive will outgrow the obesity. Although of metabolic size. Thus, to lose
therapeutic intervention. The ab- obesity at any time in life may predis- weight or to maintain a given weight,
sence of such morbidity indicates that pose to adiposity-related morbidity, the obese child may need to restrict
a more conservative therapeutic ap- the risks and futility of weight reduc- food intake to a point socially unac-
proach may be taken. It is possible tion probably exceed the benefits in ceptable to the child and his or her
that certain patients may be medi- the otherwise healthy obese child. family. The pediatrician must weigh
cally healthier at a greater body Such children should be monitored the physiology against the psy-
weight than western society currently regularly for signs of adiposity-related chology of such a plan.
accepts as ideal. Before one pre- morbidity and encouraged to avoid Obesity, or the propensity to be-

PIR 54 pediatrics in review #{149} vol. 11 no. 2 august 1989

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 NUTRITION

come obese, is a disorder that is tion: Theory and Practice. London, England: milder forms of obesity.
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intervention. The irreversibility of adi- ulation of adipose tissue metabolism and D. Weight loss causes a significant decrease
pocyte hyperplasia and the increased growth: implications for the development of
in the number of adipocytes.
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E. After a child has obtained a fat cell num-
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ton, FL: CRC Press; 1989 ber exceeding that of a normal adult, he
child suggest that early detection of or she will always remain hyperplastic.
Gem SM. Continuities and changes in fatness
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Such identification should be possible 5. Which of the following is least likely to
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be a true statement?
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tissue cellularity in obese school girls before A. Twin and adoption studies show that obe-
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and after dietary treatment. Am J Clin Nutr.
to family history of obesity, and as- 1978:31:68-75 ment, not genotype.
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role in preventive medical cane by Ann Intern Med 1985;6(suppl):977-1 077 fold caliper measurement of subcuta-
Johnston FE. Sex differences in fat patterning
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C. The predominantly abdominal distribution
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Leibel AL, Edens NK, Fried 5K. Physiologic pattern.
proach to the successful manage-
basis for the control of body fat distribution D. The endocrine abnormalities demon-
ment of the obese child. The rate of in man. Annu Rev Nutr. In press strated by obese individuals normalize
recidivism remains high, and signifi- Mallick HJ. Health hazards of obesity and with weight reduction.
cant morbidity may be associated weight control in children: a review of the E. Pubarche/adrenarche tend to occur ear-
with weight-reduction therapy. Pedia- literature. Am J Public Health 1 983;73:78-
liar in obese children.
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Pugliese MT, Lifshitz F, Grad G, Fort P, Marks- 6. Which of the following causes of obesity
plex nature of obesity in childhood Katz M. Fear of obesity. N EngI J Med is typically associated with average, or
and of the risks associated with its 1 983;309:513-51 8
above average, height for age in children?
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A. Hypothyroidism.
apeutic intervention is begun, the young man after famine exposure in utero
B. Hypercortisolism (Cushing disease).
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tral nervous system growth contin- C. Reduced rate of energy expenditure as a E. Pseudohypoparathyroidism.
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Med 1 988;31 8:467-472 7. Each of the following is a true statement
must be scrutinized for the possibility
Roberts SB, Savage J, Coward WA, Chew B, pertaining to the treatment of obesity in chil-
of precipitation of anorexia nervosa Lucas A. Energy expenditure and intake in dren, except:
on bulimia. infants born to lean and overweight mothers. A. Dietary therapy should generally be di-
N Engl J Med 1988;318:461-466 rected toward slowing the rate of fat ac-
Rosenbaum M, Leibel AL. Pathophysiology of cretion rather than weight loss.
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ACKNOWLEDGMENTS
137
pervised weight reduction diets have ad-
This work was supported, in part, by Na-
verse reactions.
tional Institutes of Health grant AM30583.
C. Long-term studies of weight-reduced chil-
dren show that 80% to 90% eventually
Self-Evaluation Quiz
return to their previous weight percent-
SUGGESTED READING 4. Each of the following is a true statement, iles.
except: 0. There is no documented role for pharm-
Bouchard C. Genetic factors in the regulation
of adipose tissue distribution. Acta Paediatr A. Excessive body fat is stored by increasing acotherapy.
Scand. 1988;223 (suppl 723):135-.42 adipocyte size (hypertrophy) and/or num- E. Potential morbidity related to obesity is
Dietz WH. Nutrition and obesity. In Grand RJ, ber (hyperplasia). an indication for more aggressive thera-
Sutphen JL, Dietz WH, eds. Pediatric Nutri- B. Hypertrophy of fat cells predominates in peutic intervention.

pediatrics in review #{149} vol. 11 no. 2 august 1989 PIR 55

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 Obesity in Childhood
Michael Rosenbaum and Rudolph L. Leibel
Pediatr. Rev. 1989;11;43-55
DOI: 10.1542/pir.11-2-43

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