Obese (ob/ob) mice and rats with VMH-lesions become obese even if pair-fed to their respective controls. These animals must therefore expend less energy than normal. Our overall goal is to identify mechanisms responsible for the increased efficiency of dietary energy retention in obese animals and to understand how regulation of these processes is altered. Our working hypothesis is that low Na+, K+ ATPase in skeletal muscle and low heat output by brown adipose tissue contribute to the high retention of dietary energy, with the major thrust of the porposed studies on the latter process. Effects of diet composition and environmental temperature on sympathetic nervous system activity, as indicated by norepinephrine turnover, in brown adipose tissue and selected other organs of lean and obese animals will be examined. Because thermogenin appears to be the unique protein in brown adipose tissue that permits high heat production upon sympathetic stimulation we will also assay the availability of this protein in brown adipose tissue mitochondria by the -3H-GDP binding procedure. The role of adrenal corticosterone and adrenal catecholamines in induction of hyperphagia, in control of Na+, K+ ATPase in skeletal muscle and in brown adipose tissue metabolism in obese mice and rats will be evaluated. Comparisons of obese (ob/ob) mice and rats with hypothalamic lesions should help identify key metabolic events that permit high retention of dietary energy in these animals. These data should increase our understanding of the metabolic basis for development of obesity and should aid us in developing improved nutritional approaches to cope with the prevention and control of obesity.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Nutrition Study Section (NTN)
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Michigan State University
Sch of Home Econ/Human Ecology
East Lansing
United States
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Mistry, Anahita M; Swick, Andrew G; Romsos, Dale R (2004) Leptin acts peripherally to limit meal-induced increases in plasma insulin concentrations in mice: a brief communication. Exp Biol Med (Maywood) 229:1033-7
Lee, Joo-Won; Swick, Andrew G; Romsos, Dale R (2003) Leptin constrains phospholipase C-protein kinase C-induced insulin secretion via a phosphatidylinositol 3-kinase-dependent pathway. Exp Biol Med (Maywood) 228:175-82
Lee, Joo-Won; Romsos, Dale R (2003) Leptin administration normalizes insulin secretion from islets of Lep(ob)/Lep(ob) mice by food intake-dependent and -independent mechanisms. Exp Biol Med (Maywood) 228:183-7
Mistry, Anahita M; Romsos, Dale R (2002) Intracerebroventricular leptin administration reduces food intake in pregnant and lactating mice. Exp Biol Med (Maywood) 227:616-9
Lee, J W; Romsos, D R (2001) Leptin-deficient mice commence hypersecreting insulin in response to acetylcholine between 1 and 2 weeks of age. Exp Biol Med (Maywood) 226:906-11
Jang, M; Mistry, A; Swick, A G et al. (2000) Leptin rapidly inhibits hypothalamic neuropeptide Y secretion and stimulates corticotropin-releasing hormone secretion in adrenalectomized mice. J Nutr 130:2813-20
Mistry, A M; Swick, A; Romsos, D R (1999) Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice. Am J Physiol 277:R742-7
Jang, M; Romsos, D R (1998) Neuropeptide Y and corticotropin-releasing hormone concentrations within specific hypothalamic regions of lean but not ob/ob mice respond to food-deprivation and refeeding. J Nutr 128:2520-5
Mistry, A M; Swick, A G; Romsos, D R (1997) Leptin rapidly lowers food intake and elevates metabolic rates in lean and ob/ob mice. J Nutr 127:2065-72
Chen, N G; Swick, A G; Romsos, D R (1997) Leptin constrains acetylcholine-induced insulin secretion from pancreatic islets of ob/ob mice. J Clin Invest 100:1174-9

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