Sex differences and the roles of sex steroids in energy intake regulation and high-fat diet preference during free-choice feeding in young adult rats.

Excessive intake of high-fat diet (HFD) contributes to obesity. Sex differences and the specific roles of sex steroids in regulating HFD preference, particularly in metabolically flexible young animals, remain poorly understood. We first examined energy intake in young (starting age: 8 weeks old) gonadally intact male and female rats provided with ad libitum access to either a normal diet (ND) or an HFD alone for 30 days, without a dietary choice. Energy intake did not differ between ND-fed and HFD-fed rats in either sex. Therefore, we hypothesized that the lack of a dietary choice may mask the preference for HFD. In the next experiment, young rats were assigned to six groups: gonadally intact males (M) and females (F), sham-operated (Sham) or orchiectomized (ORX) males, and ovariectomized females with or without estradiol replacement (E2(+), E2(-)). Animals received either ND alone or concurrent access to ND and HFD for 30 days. HFD preference was significantly greater in the M than in the F group. HFD preference and total energy intake were greater in the M and Sham groups than in the ORX group when provided with HFD. In contrast, HFD preference did not differ among the F, E2(-), and E2(+) groups, although E2 deficiency increased total energy intake regardless of diet condition. Chronic neuronal activity was assessed via ΔFosB expression in the nucleus accumbens (NAc). ΔFosB expression in the NAc was significantly higher in the HFD-fed than in the ND-fed rats in the M group. These results suggest that androgens play a critical role in enhancing HFD preference and excessive energy intake under free-choice conditions in young adult male rats. In contrast, under the present experimental conditions, estrogens primarily regulate total energy intake but do not affect HFD preference, suggesting mechanistically distinct pathways for dietary choice between sexes.