Unit on Growth and Obesity
Developmental Endocrinology Branch, NICHD
La Bassin des Tuileries by Picasso (Private
Collection, Grosse Pointe , MI
UGO Site Map
Unit on Growth and Obesity Clinical Studies
How
to contact the UGO
to refer a patient
Pediatric
Endocrinology and Obesity Links
Other
NICHD Pediatric Endocrine Protocols
Current Research
Eat
Well, by Robbie Kraff. Reproduced with permission
Functional Statement for the UGO:
This
unit investigates the genetic, physiologic, metabolic, behavioral, and
environmental factors involved in determining weight regulation and body
composition, with a special emphasis on pediatric and minority populations. This unit actively investigates the causes
and treatment of obesity in children and adults, and studies the impact of body
composition and body fat redistribution on the metabolic complications of
obesity. Both clinical and basic studies
are employed to develop novel approaches to the prevention and treatment of
obesity.
Objectives
1.
To investigate the genetic, physiologic,
metabolic, behavioral, and environmental characteristics
leading to obesity in diverse
2.
To devise population-specific risk predictors
to enable identification of children
and adults at risk for the
development of obesity and its complications.
3.
To study the role of nutrient
partitioning in development of metabolic syndromes
4.
To use this information to develop
rational interventions specifically targeted to prevent and treat obesity.
Introduction
Many minority populations in the
Results
Different factors may account
for the comorbid conditions associated with obesity an African Americans and
Caucasians. Intra-abdominal adipose tissue (also called
visceral abdominal adipose tissue) is generally believed to be of great
importance as a cause of the complications of obesity (such as high blood
pressure and Type 2 diabetes). We have found that African American adults and
children have significantly less intra-abdominal adipose tissue than Caucasians
of similar body weight--findings that imply the relationships between adipose
tissue depots and the complications of obesity may be different in African
Americans and Caucasians. In other
studies we have found a relationship between subcutaneous adipose tissue and
plasma insulin levels in African Americans that is not found in Caucasians and
greater free insulin-like growth factor levels in African Americans. Ongoing natural history studies explore the
etiology and consequences of these differences in body composition and hormone
levels.
The greater susceptibility
for weight gain of African Americans may result from differences in metabolic
efficiency: We have found that resting energy expenditure
is approximately 90 kcal/d less in African American than in Caucasian
children. Ongoing studies explore the
role of these differences in energy expenditure in predicting future weight
gain.
A pair of melanocortin 3
receptor polymorphisms are associated with childhood body weight. Among 355 overweight and
non-overweight children, 8.2% were double homozygous for a pair of missense
MC3R sequence variants (Thr6Lys and Val81Ile).
Such children were significantly heavier (BMI and 
< 0.0001), had more body fat (body
fat mass and percentage fat mass; p < 0.001) and had greater plasma leptin
(p < 0.0001) and insulin concentrations (p < 0.001) and greater insulin
resistance (p<0.008) than wild type or heterozygous children. Both sequence variants were more common in
African American than Caucasian children. In vitro expression studies found the
double mutant MC3R was partially inactive, with significantly fewer receptor
binding sites, decreased signal transduction and less protein expression.
Diminished MC3R expression in this double MC3R variant may be a predisposing
factor for excessive gain in body weight in children.
 |
|
| Immunofluorescence of MC3R –GFP fusion proteins |
Typical Winter Holiday weight
gain in adults is only 0.37 kg (0.8 lb).
In a study of 200
Caucasian, African American, Hispanic, and Asian adults in which subjects did
not know that the primary outcome measure was body weight, we found that weight
gain from Thanksgiving Day to New Year's Day was only 0.37 kg, far less than
the 2.27 kg (5 lb) commonly believed.
Winter holiday weight gain may be a major contributor to annual weight
gain in adults.
Binge eating in children is
associated with greater food intake as well as high body weight and adiposity. Children who report episodes of loss
of control over eating weigh more and have more body fat than those who do not
report such episodes, gain weight more rapidly over time, and eat more during
laboratory test meals.
Orlistat treatment in the
context of a behavioral modification program may help significantly overweight
adolescents lose weight. Over a 3-month treatment period, 20
adolescents decreased their body weight by an average of 3.8%. Orlistat was well tolerated, and was
associated with decreases in total and LDL-cholesterol. Its efficacy versus a behavior modification
is currently being explored in a randomized, placebo-controlled double-blind,
study.
To refer a
patient, contact a study coordinator:
|
Non-Exercise
Activity Thermogenesis in Overweight children |
Lean
African American and Caucasian children |
Overweight
Women |
Children
and Adults with WAGR Syndrome (all ages) |
Obese
and Normal Weight Men an d Women for studies of body heat during exercise |
|
Mary
Roberts, MD |
Jennifer
Gustafson, BS |
Lisa
Yanoff, MD |
Joan
Han, MD and Rebecca Levinn, BA |
David
Savastano, PhD |
|
National Institutes of Health Building 10, Room 1E-3330 10 Center Drive, MSC 1103 Bethesda, MD
20892-1103 |
National Institutes of Health Building 10, Room 1E-3330 10 Center Drive, MSC 1103 Bethesda, MD
20892-1103 |
National Institutes of Health Building 10, Room 1E-3330 10 Center Drive, MSC 1103 Bethesda, MD
20892-1103 |
National Institutes of Health Building 10, Room 1E-3330 10 Center Drive, MSC 1103 Bethesda, MD
20892-1103 |
National Institutes of Health Building 10, Room 1E-3330 10 Center Drive, MSC 1103 Bethesda, MD
20892-1103 |
|
TEL: 301-594-1176 |
TEL: 301-496-4168 |
TEL: 301-451-3820 |
TEL: 301-435-7820 |
TEL: 301-496-6726 |
|
FAX: 301-480-2650 |
FAX: 301-480-2650 |
FAX: 301-480-2650 |
FAX: 301-402-0574 |
FAX: 301-480-2650 |
Unit on Growth
and Obesity Current Clinical Studies
96-CH-0101: Population Differences in the Insulin
Sensitivity, Resting Energy Expenditure, and Body Composition of Overweight
Children and Children of Overweight Parents.
This natural history project
studies metabolic, psychosocial, and genetic factors that may be important for
childhood obesity in 450 African American and Caucasian prepubertal children
who are being followed for 15 years, into adulthood.
98-CH-0111: Safety and efficacy of orlistat (Xenical™,
Hoffmann LaRoche) in African American and Caucasian children and adolescents
with obesity-related comorbid conditions.
Orlistat is a medication
that, in adult studies, has decreased body weight. It also appears to have
favorable effects on obesity-related comorbid conditions like hypertension,
hypercholesterolemia, and impaired glucose tolerance. We are determining the safety and efficacy of
orlistat for reducing obesity-related comorbidities using a randomized,
double-blind, placebo-controlled clinical trial in 200 adolescents.
00-CH-0134:
Effects of Metformin on body weight, energy intake, and energy expenditure of
overweight children. Metformin, a medication that suppresses hepatic
glucose production, appears to stabilize or decrease body weight in overweight
children, but how metformin causes weight loss is unknown. We are studying how metformin affects body
weight, energy intake and energy expenditure using a randomized, double-blind,
placebo-controlled clinical trial in 100 children.
00-CH-0180: Obesity in the WAGR syndrome. WAGR (Wilms
tumor, Aniridia, Genitourinary abnormalities and mental Retardation)
syndrome is caused by haploinsufficiency for genes on chromosome 11p. Some
patients with WAGR have severe, early-onset obesity. In collaboration with the International
WAGR syndrome Association http://www.wagr.org/ we are studying the importance of
brain-derived neurotrophic factor, a gene found on 11p, as a cause of the
obesity seen in children with WAGR syndrome.
04-CH-0050: Eating Behavior in
children. This natural history project studies
actual food intake in the laboratory setting in children who describe
particular eating styles (such as binge eating) and examines the genetic links
between eating styles, food intake, and genetic polymorphisms.
06-CH-0038: Body Heat Content and Dissipation in Obese and Normal
Weight Adults. Overweight adults have difficulty sustaining
high intensity exercise, in part because of rapid heat generation. This project
studies how heat is dissipated in obese and non-overweight adults at rest and
during exercise.
06-CH-0039: Pilot Program for the Targeted Prevention of
Adolescent Weight Gain. It remains unclear how best to help
adolescents at-risk for adult obesity avoid weight gain. This project compares
the efficacy of interpersonal therapy as a strategy to help girls manage their
weight.
06-CH-0141: Non-exercise Activity Thermogenesis (NEAT) in
Children. Overweight children appear to spend less time
being physically active. This project studies ways to help children be more
active, examining ways to increase the energy burned while fidgeting.
07-CH-0126: Pilot Study of the Metabolic Effects of Betahistine
Hydrochloride in Overweight Women. Several studies in animals suggest that
histaminergic receptors in the central nervous system appear to influence food
intake. This project studies whether betahistine, a histamine 3 receptor and
histamine 1 receptor agonist, can decrease food intake acutely in humans.
Unit Personnel Photos
Unit on Growth and Obesity Lab Party, June 2007
Unit on Growth and Obesity Lab meeting, May 2006
Unit on Growth and Obesity Lab Party, June, 2005
Unit on Growth and Obesity lab party, June 2004
Address for Unit Staff:
Unit
on Growth and Obesity, Developmental Endocrinology Branch
NICHD, National Institutes of Health
Hatfield Clinical
Tel 301-4964686, Fax 301-402-0574
Unit Personnel Email Addresses
|
Head: Jack A.
Yanovski, MD, PhD |
|
|
Unit Staff |
|
|
Lisa
Yanoff, MD |
|
|
Mary
Roberts, MD |
|
|
Joan Han,
MD |
|
|
David
Savastano, PhD |
|
|
Diane
Adler-Wailes, MS |
|
|
Sheila
Brady, RN, PNP |
|
|
Lisa
Ranzenhofer, BS |
|
|
Jennifer
Gustafson, BS |
|
|
Rebecca
Levinn, BA |
|
|
Jenna
Checchi, BS |
|
|
Rachael
Sorg, BA |
|
|
Natasha
Schvey, BA |
|
|
Ethan
Sanford, BS |
|
|
Collaborators at the NIH |
|
|
Van
S. Hubbard, MD, PhD |
|
|
Jonathan
Krakoff, MD |
|
|
|
|
|
James
Reynolds, MD |
|
|
Alexander
Gorbach, PhD |
|
|
Constantine
Londos, PhD |
|
|
Vincent
Manganiello, PhD |
|
|
Susan Z.
Yanovski, MD |
|
|
Margaret
Keil, RN, PNP |
|
|
Nancy
Sebring, MEd, RD |
|
|
Christine
Salaita, MS, RD |
|
|
Merel
Schollnberger, MS, RD |
|
|
Blakeley
Denkinger, MPH, RD |
|
|
Karim
Calis, Pharm. D. |
|
|
Bart
Drinkard, P.T. |
|
|
Collaborators in the |
|
|
Marian
Tanofsky-Kraff, PhD |
|
|
Nazrat
Mirza, MD |
|
|
|
|
Selected Recent Publications 2000 -
2007
Yanovski JA, Diament AL, Sovik KN, Nguyen,
TT, Li H, Sebring N, Warden CH. Associations between
Uncoupling Protein 2, body composition, and resting energy expenditure in lean
and obese African American, White, and Asian children. Am J Clin Nutr. 71(6): 1405-1420, 2000.
Yanovski, JA, Yanovski, SZ, Sovik KN,
Nguyen TT, O’Neil PM, Sebring N. A
Prospective Study of Holiday Weight Gain. N. Engl. J. Med. 342(12): 861-7, 2000.
Nguyen TT, Keil MF, Russell DL,
Pathomvanich, A, Uwaifo GI, Sebring NG, Reynolds JC, Yanovski JA. Relation of acanthosis nigricans to
hyperinsulinemia in overweight African American and white children. J Pediatr. 138(4):474-480, 2001.
Russell DL, Keil MF, Bonat SH, Uwaifo GI,
Nicholson JC, McDuffie, JR, Hill
SC
Drinkard B, McDuffie J, McCann S, Uwaifo G,
Nicholson J, Yanovski JA. Walk/run performance in overweight adolescents. Physical Therapy 81(12):1889-1896, 2001.
Uwaifo GI, Nguyen TT, Russell, DL, Keil MF,
Nicholson JC, Bonat SH, McDuffie, JR, Yanovski JA. Differences in Insulin Secretion and
Sensitivity of Caucasian and African American Prepubertal Children. J Pediatr. 140(6):673-80, 2002.
Uwaifo, IG, Parikh SJ, Keil, M. Elberg, J.,
Chin, J, Yanovski, JA. Comparison of insulin sensitivity, clearance and
secretion estimates using euglycemic and hyperglycemic clamps in children. J
Clin Endocrinol Metab 87: 2899–2905, 2002.
Morgan CM, Yanovski SZ, Nguyen TT, McDuffie
J, Sebring N, Jorge M, Keil M, Yanovski JA.
Loss of control over eating, adiposity, and psychopathology in
overweight children. Int J Eat Disord. 31:430-441, 2002.
McDuffie, JR, Calis, KA, Uwaifo, GI, Sebring , NS
McDuffie, JR, Calis, KA, Booth, S, Uwaifo,
GI, Yanovski, JA. Effects of orlistat on
fat-soluble vitamins in obese adolescents.
Pharmacotherapy 22(7):814-22, 2002.
Bonat, SH, Pathomvanich, A, Keil MF, Field,
AE, Yanovski JA. Self-assessment of
pubertal maturation in overweight children. Pediatrics 110:743–747, 2002.
Yanovski, SZ,
Yanovski, JA. Obesity. N Engl J Med
346:591-602, 2002
Yanovski
JA, Rose SR, Municchi G, et al. Treatment
with a Luteinizing Hormone-Releasing Hormone Agonist-in Adolescents with Short
Stature. New Engl. J. Med, 348: 908-917, 2003.
Feng NP, Adler-Wailes D, Elberg J, Chin J,
Fallon E, Carr A, Fraser del Llado T, Yanovski JA. Sequence Variants of the Proopiomelanocortin
(POMC) Gene and Their Associations with Body Composition in Lean and Overweight
Children. Obes Res 11:619-24, 2003.
Yanovski JA, Yanovski SZ. Treatment of Pediatric
and Adolescent Obesity. JAMA. 289:1851 -1852, 2003.
Freedman RJ, Aziz N, Albanes D, Hartman T,
Danforth D, Hill S, Sebring N, Reynolds JC, Yanovski, JA. Weight and Body Composition Changes During
and After Adjuvant Chemotherapy in Women with Breast Cancer. J Clin Endocrinol
Metab 88(5): 2248-53, 2004.
Mirza, NM, Kadow K, Palmer M, Solano H,
Rosche C, Yanovski JA. Prevalence of Overweight Among Inner City Latino
Children and Adolescents. Obes Res. Aug;12(8):1298-310, 2004.
McDuffie JR, Riggs PA, Calis KA, Freedman
RJ, Oral EA, DePaoli AM, Yanovski JA. Effects of exogenous leptin on satiety
and satiation in patients with lipodystrophy and leptin insufficiency. J Clin Endocrinol Metab. 89: 4258-4263, 2004.
McDuffie J, Adler-Wailes D, Elberg J,
Fallon E, Steinberg E, Tershakovec A, Arslanian S, Delany J, Bray G, Yanovski
JA. Prediction equations for resting energy expenditure in overweight and
non-overweight Black and White children.
Am J Clin Nutr. 80: 365-373, 2004.
McDuffie JR, Calis KA, Uwaifo GI, Freedman,
RJ, Sebring NG, Fallon EM, Frazer TE, Hubbard VS, Yanovski JA. Efficacy of
orlistat as an adjunct to behavioral treatment in overweight African American
and Caucasian adolescents with obesity-related co-morbid conditions. J Pediatr
Endocrinol Metab. 17:307-319, 2004.
Tanofsky-Kraff M, Yanovski SZ, Wilfley DE
Parikh SJ, Edelman M, Uwaifo GI, Freedman,
RJ, Semega-Janneh M, Reynolds J, Yanovski JA. The relationship between obesity
and serum 1, 25 dihydroxy Vitamin D concentrations in healthy adults. J Clin
Endo Metab 89(3): 1196-9, 2004.
Adler-Wailes DC, Liu H, Ahmad F, Feng N,
Londos C, Manganiello V, Yanovski JA. Effects of the HIV-protease inhibitor
ritonavir on catecholamine-stimulated lipolysis. J
Clin Endocrinol Metab. 2005 Jun;90(6):3251-61.
Norman AC, Drinkard B, McDuffie JR,
Ghorbani S, Yanoff LB, Yanovski JA. The
Influence of Excess Adiposity on Exercise Fitness and Performance in Overweight
Children and Adolescents. Pediatrics 115(6): e690-6, 2005.
Cohen ML, Tanofsky Kraff M, Young-Hyman D,
Yanovski JA. Weight and Its Relationship
to Adolescent Perceptions of their Providers (WRAP): A Qualitative and
Quantitative Assessment of Teen Weight-Related Preferences and Concerns. J Adol
Health 7(2): 163e9-16, 2005.
Feng NP, Young SF, Aguilera G, Puricelli E,
Adler-Wailes DC, Sebring NG, Yanovski JA. Partial inactivation of the
melanocortin 3 receptor in pediatric-onset obesity. Diabetes 54:2663–2667, 2005.
Robotham DR, Schoeller DA, Mercado AB,
Mirch MC, Theim KR, Reynolds JC, Yanovski JA.
Estimates of Body Fat in Children by Hologic QDR-2000 and QDR-4500A Dual-Energy
X-ray Absorptiometers Compared With Deuterium Dilution. J Ped Gastroenterol
Nutr. 42: 331-335, 2006.
Tanofsky-Kraff M, Cohen ML,
Yanovski SZ, Cox C, Theim KR, Keil M, Reynolds JC, Yanovski JA. A prospective study of psychological
predictors of body fat gain among children at high risk for adult obesity. Pediatrics 117: 1203-1209, 2006.
Yanoff LB, Parikh SJ, Spitalnik A,
Denkinger B, Sebring NG, Remaley AT, Yanovski JA. High Prevalence of Hypovitaminosis D and
Secondary Hyperparathyroidism in Obese Black Americans. Clin Endocrinol
(Oxf);64(5):523-9, 2006.
Tanofsky-Kraff M, Rahimi A, Yanovski S,
Ranzenhofer L, Roberts M, Theim K, Menzie C, Mirch M, Yanovski JA. Differences
between the Perceived and Actual Age of Overweight Onset in Children and Adolescents. Medscape General Medicine Clinical Nutrition
and Obesity; 8(3):1-5, 2006.
Taylor ED, Theim KR, Mirch MC, Ghorbani S,
Tanofsky-Kraff M., Adler-Wailes DC, Brady S, Reynolds JC, Calis KA, Yanovski
JA. Orthopedic complications of overweight in children and adolescents.
Pediatrics, 117:2167-2174, 2006.
Mirch M, McDuffie
J, Yanovski S, Schollnberger M, Tanofsky-Kraff M, Theim K, Krakoff, J, Yanovski
JA. Effects of binge eating on
satiation, satiety, and energy intake of overweight children. Am J Clin Nutr.84:732-8, 2006.
El-Gharbawy A, Adler-Wailes DC, Mirch MC,
Theim KR, Ranzenhofer LM, Tanofsky-Kraff M, Yanovski JA. Serum brain-derived
neurotrophic factor concentrations in lean and overweight children and
adolescents. J Clin Endocrinol Metab. 91(9): 3548-52, 2006.
Young-Hyman D, Tanofsky-Kraff M, Yanovski SZ, Keil M,
Cohen ML, Peyrot M, Yanovski JA. Psychological status and weight-related
distress in overweight or at risk for overweight children.
Obesity 14(12):2249-58,
2006.
Ning C, Yanovski JA. Endocrine disorders associated with pediatric
obesity. Handbook of Pediatric Obesity.
Goran MI and Sothern MS, eds. CRC
Press,Boca Raton, FL, Chapter 9: 135-155, 2006
Gray J, Yeo GSH, Cox JJ, Morton J, Adlam
ALR, Keogh JM, Yanovski JA, El Gharbawy A, Han JC, Tung YCL, Hodges JR, Raymond
FL, O’Rahilly S, Farooqi IS.
Hyperphagia, severe obesity, impaired cognitive function and
hyperactivity associated with functional loss of one copy of the BDNF
gene. Diabetes 55:3366–3371, 2006.
Glasofer DR, Tanofsky-Kraff M,
Eddy KT, Yanovski SZ, Theim KR, Mirch MC, Ghorbani S, Ranzenhofer LM, Haaga D,
Yanovski JA. Binge eating in overweight,
treatment-seeking, adolescents. J Pediatr Psychol 32(1): 95-105, 2007.
Tanofsky-Kraff
M, Haynos AF, Kotler LA, Yanovski SZ, Yanovski JA. Laboratory-Based
Studies of Eating during Meals among Children and Adolescents. Curr. Nutr. Food Sci. 3, 55-74, 2007.
Theim, K, Tanofsky-Kraff M, Salaita CG,
Haynos AF, Mirch MC, Ranzenhofer LM, Yanovski SZ, Wilfley DE, Yanovski JA. Children’s descriptions of the foods consumed
during episodes of loss of control eating.
Eat Behav 8:258-265, 2007.
Fleisch AF, Agarwal N, Roberts MD, Han JC,
Theim KR, Vexler A, Troendle J, Yanovski SZ, Yanovski JA. Influence of serum leptin on weight and body
fat growth in children at high risk for adult obesity. J Clin Endocrinol Metab
92:948-954, 2007.
Tanofsky-Kraff M, Theim KR, Yanovski SZ,
Bassett AM, Burns NP, Ranzenhofer LM, Glasofer DR, Yanovski JA. Validation of
the emotional eating scale adapted for use in children and adolescents (EES-C).
Int J Eat Disord 40:232-240, 2007.
Sebring, NG, Denkinger BI, Menzie CM,
Yanoff LB, Parikh SJ, Yanovski JA.
Validation of three food frequency questionnaires to assess dietary
calcium intake in adults. J Am Diet
Assoc. 107: 752-9, 2007.
Yanoff LB, Menzie CM, Denkinger BI, Sebring
NG, McHugh T, Remaley AT, Yanovski, JA.
Inflammation and iron deficiency in the hypoferremia of obesity. Int J
Obes. 31:1412-19, 2007.
Links to Web Sites
Developmental Endocrinology Branch: http://eclipse.nichd.nih.gov/nichd/deb/
LWPES (Lawson-Wilkins Pediatric Endocrine
Society: http://www.lwpes.org/
AAP (
SPR (Society for Pediatric Research): http://www.aps-spr.org
The Endocrine Society: http://www.endo-society.org
Obesity
Web Sites
NIDDK's Weight Control Information
Network: http://win.niddk.nih.gov/index.htm
Body Mass Index Charts: http://www.cdc.gov/nchs/about/major/nhanes/growthcharts/charts.htm
The Obesity Society, NAASO (North American
Association for the Study of Obesity) Web site:
http://www.naaso.org
IASO (International Association for the Study
of Obesity): http://www.iaso.org
Obesity (formerly Obesity Research)
Journal: http://www.obesityresearch.org
American Journal of Clinical Nutrition: http://www.ajcn.org/
The International Journal of Obesity: http://www.nature.com/ijo/
The International Journal of Pediatric
Obesity: http://www.tandf.co.uk/journals/titles/17477166.asp
Contacts for other pediatric
endocrine conditions studied by the NICHD or NIDDK:
Carney complex /
PPNAD
|
Dr. C. Stratakis
|
stratakc@mail.nih.gov
|
Pediatric
Pituitary and Adrenal Tumors
|
Dr. C. Stratakis
|
stratakc@mail.nih.gov
|
Congenital
adrenal hyperplasia
|
Dr. D. Merke
|
merked@mail.nih.gov
301-496-0718 |
Children with
short stature
|
Dr. J. Baron
|
jbaron@mail.nih.gov
|
Children with
Diabetes
|
Dr. K. Rother
|
kristinaR@mail.nih.gov
http://intramural.niddk.nih.gov/research/faculty.asp?People_ID=1663 |
Last Revised: 9/5/07