Differential effects of NE, CLON, and 5-HT on feeding and macronutrient selection in genetically obese (ob/ob) and lean mice.

The effects of central injection of norepinephrine (NE), clonidine (CLON), and 5-hydroxytryptamine (5-HT) on feeding and macronutrient selection in genetically obese (C57B1/6J, ob/ob) and lean mice (C57B1/6J, +/?) were examined. Mice were adapted to single-energy source diets of carbohydrate, protein, and fat and then injected with NE (20-80 nmol) or CLON (5-20 nmol) immediately prior to dark onset (17h00). Measurements of nutrient intake were determined 2 h postinjection. In a separate study, obese and lean mice were deprived of food for 1 h (1700-1800) and subsequently treated with 5-HT (35-140 nmol). The results of this study demonstrate that the hyperphagic effect of NE and CLON and the anorectic effect of 5-HT are dose dependent and nutrient selective. Specifically, at the onset of the nocturnal cycle, obese and lean mice exhibit a shift in diet choice resulting in an increased preference for carbohydrate and a reduction in the proportional intake of protein and fat. At this time, central injection of NE or CLON potentiates an already enhanced preference for carbohydrate; whereas injection of 5-HT suppresses carbohydrate intake (kcal) in both phenotypes without altering fat or protein intake. However, in comparison to lean mice, obese mice showed significantly augmented hyperphagic responses to NE and CLON administration but decreased inhibition of feeding after 5-HT injection. This suggests that the stimulatory effect of alpha 2-noradrenergic mechanisms controlling feeding and carbohydrate ingestion is enhanced in obese mice, while the inhibitory influence of serotonergic mechanisms is attenuated.