Neurochemical and Hormonal Changes in Lean and Obese Zucker Rats During 48 Hours of Calorie Deprivation. Are They...

Lean and obese Zucker rats were deprived of food for 12, 24, and 48 h. After sacrifice, plasma and brain tissue were saved for hormone and regional hypothalamic monoamine analysis. An ad libitum group was killed at time 0 for comparison to the food deprived groups. Insulin (I), C-peptide (CP), glucose, and the CP/I ratio were dramatically different across phenotype. Glucagon was only different at 12 h of caloric deprivation. Insulin secretion dropped substantially with fasting as reflected by the decrease in C-peptide plasma levels in both lean and obese rats. The CP/I ratio, which indicates clearance of insulin, increased in lean rats across time of fasting but did not significantly change in obese rats. Several distinct changes occurred between phenotypes in the hypothalamus across food deprivation. Lateral hypothalamic 5HT content and 5HT turnover (5HIAA/5HT) increased in lean but not obese rats during the period of fasting. Likewise ventromedial hypothalamic dopamine turnover (NE/DA) decreased during caloric deprivation in lean rats but not in the obese rats. This same turnover was increased in the PVNA of obese but not lean rats during caloric deprivation. Individual measurements of both C-peptide and insulin correlated significantly with LH 5HT turnover and VMH dopamine turnover in lean rats but not obese rats. These data suggest that obese rat's hypothalami may possibly be insensitive to insulin or some factor such as leptin that insulin may regulate. Because obese rats cannot change their levels of hypothalamic neurotransmitters when insulin or some other insulin induced factor changes, may suggest clues as to why these rats became obese. Perhaps these data may help explain the altered body weight set-point, increased adiposity, and hyperphagia in these animals.