The underlying causes of obesity in man are still not known. Therefore it is extremely difficult to prevent or permanently cure obesity. It is unlikely that obesity in man is a single entiry. In experimental animals evidence separately implicates pancreatic and adrenal function, decreased sympathetic tone, physical inactivity, diet composition and, of course, adipose tissue development. We plan to study these factors in two different animals models of obesity: genetically obese Zucker rats and in Osborne-Mendel rats made obese on palatable diets. The specific experiments include: 1. Examining the influence of the central nervous system (CNS) on pancreatic insulin hypersecretion in obesity using a perfused rat pancreatic preparation in which the CNS innervation is left intact; Evaluating the effects of phentolamine (an alpha adrenergic blocker), propranolol (a beta adrenergic blocker) and atropine (an inhibitor of the parasympathetic nervous system). 2. Studying insulin release in preobese rats in isolated perfused pancreata. 3. Studying the effects of adrenalectomy (ADX) on development of adiposity (using osmium fixation technique) and protein turnover in Zucker obese rats; Studying glucose metabolism and insulin sensitivity in skeletal muscle using a hind limb perfusion system in ADX obese and lean Zucker rats fed a high fat diet; Studying possible alterations in taste, preference and/or caloric regulation with ADX. 4. Evaluating the contribution of various tissues to the thermic effect of a high carbohydrate or high fat meal (as measured by blood flow) in genetically obese rats, in rats made obese on high fat diets and in obesity resistant rats. 5. Studying how exercise termination effects norephineprine turnover and activity of catecholamine synthesizing enzymes--tyrosine hyroxylase and dopamine beta hydroxylase; Investigating effects of exercise termination and high fat diets on adipocyte proliferation by measuring 3H-thymidine incorporation into adipocyte DNA. 6. Exploring the effects of treadmill exercise of different intensity and duration in male and female rats on food intake and metabolic responses to exercise termination including body composition, adipose cellularity, lipoprotein lipase activity in white and brown adipose tissues well as citrate synthase activity in muscle.
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