The prevalence of obesity in the U.S. ranges from 25% overall to greater than 50% in some minority groups. Obesity may constitute the most common health problem in America, with associated morbidity and mortality rates equal to that of cancer. However, therapeutic options remain largely ineffectual. Thus, research into the pathophysiology and treatment of obesity assumes great significance to national health. Recent studies have demonstrated the importance of the brain, and specifically hypothalamus, to the regulation of body weight. Several hypothalamic substances have been identified which dramatically alter appetite and metabolic rate. In the present study, we have chosen to investigate the role of one particularly interesting hypothalamic neuropeptide, melanin concentrating hormone (MCH). Toward this end, transgenic mouse strains overexpressing the MCH gene will be produced. These strains should provide information regarding the physiologic actions of MCH in body weight regulation. In addition, the transgenic mice may constitute useful models for examining the actions of potential anti-obesity treatments. As an alternative approach, the effects of MCH administration by direct intracerebral injection will be studied. Dr. Ludwig's main research area is the neuroendocrine control of appetite and metabolism. In particular, he is interested in understanding how abnormal structure and function of the hypothalamus may underlie body weight disorders. The project will be conducted in the Division of Endocrinology and Metabolism of Beth Israel Hospital, Boston, under the supervision of Dr. Jeffrey Flier (Division Chief). Obesity and diabetes comprise the predominant research focus of the Division. Specific projects involve studies of insulin signal transduction, brown adipose tissue function, and leptin. The research environment contains state-of-the-art molecular biology, animal research, and transgenic facilities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
7K08DK002440-04
Application #
6175984
Study Section
Special Emphasis Panel (SRC)
Program Officer
Hyde, James F
Project Start
1997-04-15
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
4
Fiscal Year
2000
Total Cost
$120,960
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Pereira, Mark A; Jacobs Jr, David R; Van Horn, Linda et al. (2002) Dairy consumption, obesity, and the insulin resistance syndrome in young adults: the CARDIA Study. JAMA 287:2081-9
Ludwig, David S (2002) The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease. JAMA 287:2414-23
Ludwig, D S; Tritos, N A; Mastaitis, J W et al. (2001) Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 107:379-86
Ludwig, D S; Peterson, K E; Gortmaker, S L (2001) Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 357:505-8
Ludwig, D S; Ebbeling, C B (2001) Type 2 diabetes mellitus in children: primary care and public health considerations. JAMA 286:1427-30
Agus, M S; Swain, J F; Larson, C L et al. (2000) Dietary composition and physiologic adaptations to energy restriction. Am J Clin Nutr 71:901-7
Spieth, L E; Harnish, J D; Lenders, C M et al. (2000) A low-glycemic index diet in the treatment of pediatric obesity. Arch Pediatr Adolesc Med 154:947-51
Ludwig, D S (2000) Dietary glycemic index and obesity. J Nutr 130:280S-283S
Ludwig, D S; Majzoub, J A; Al-Zahrani, A et al. (1999) High glycemic index foods, overeating, and obesity. Pediatrics 103:E26
Tritos, N A; Vicent, D; Gillette, J et al. (1998) Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus. Diabetes 47:1687-92

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