Estradiol and body weight during temporally targeted food restriction: Central pathways and peripheral metabolic factors

We used temporally-targeted food restriction (TTFR), in which ovariectomized rats had chow only for 2 h/day, to test the hypothesis that estradiol benzoate (EB) suppresses feeding and decreases body weight during brief (4 day) TTFR, as it does during ad libitum feeding. All rats lost weight during TTFR, but the loss was greater with EB treatment. However, OIL and EB-treated rats ate comparable amounts of chow during TTFR. We next investigated central nervous system pathways and peripheral hormonal and metabolic changes that accompany the effects of TTFR to determine the mechanism for this effect. Immunolabeling for fos in the nucleus of the solitary tract, the terminal site of vagal afferents from the gastrointestinal tract, was increased when rats on TTFR had access to chow for 1 h on the test day, indicating neuronal activation associated with consumption of the meal. However, fos immunolabeling was not affected by EB treatment, nor were numbers of the α subtype of estrogen receptors. TTFR had the expected effects on carbohydrate and lipid metabolites and metabolic hormones, with only slight differences in plasma glucose, triglycerides, and free fatty acids attributable to EB treatment. Interestingly, plasma corticosterone levels were greater in EB-treated rats on TTFR, and increased further after eating. Given that corticosterone affects metabolism, these findings suggest that elevated corticosterone may explain the persistence of EB-induced differences in body weight during TTFR despite the lack of effect on food intake.