Female rats are relatively more sensitive to reduced lipid versus reduced carbohydrate availability

Because females have blunted counterregulatory responses to hypoglycemia relative to males, we hypothesized that females would have greater sensitivity to changes in lipid availability.

To assess this, we examined the feeding response to glucoprivation (2-deoxyglucose; 2DG) and lipoprivation (mercaptoacetate; MA) in age-matched male and female Long-Evans rats.

Males versus females had significantly greater food intake after 250 mg kg(-1) of 2DG, but there were no sex differences with the 750 mg kg(-1) dose of 2DG. Glucose responses to 250 mg kg(-1) of 2DG were also significantly greater in males versus females. In contrast, females had a significant increase in food intake with all doses of MA versus saline, and had significantly greater food intake compared with males at the lowest and highest doses of MA with a trend towards significance with the intermediate dose. To determine whether estradiol (E2) is the mechanism underlying this sexual dimorphism, ovariectomized females were injected with vehicle or 2 μg of E2 every fourth day to mimic the variations in across the estrous cycle. Ovariectomized females significantly increased feeding and glucose after 250 mg kg(-1) of 2DG over intact females and E2 had no effect on these responses. Although the feeding response to 2DG was not different, the glucose response to 2DG was still significantly greater in males versus ovariectomies females. However, ovariectomized females also did not increase food intake after MA, regardless of E2 treatment.

These data collectively suggest that males are relatively more sensitive to glucose deprivation and females are relatively more sensitive to lipid deprivation. Further, these data rule out a role for cyclic changes in E2 in these sex differences.