Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice

Abstract

Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice.

Sex differences in the response to dietary restriction in rodents

“…Clearly this disparity between sexes and types of behavior and how it relates to metabolic outcomes and aging among others requires further study. Gonadal sex hormones have been proposed to mediate the sex differences in food anticipatory activity (FAA) in rodents [46]. Recent studies have observed sex differences in FAA, but in a follow-up there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA [46].…”

“…Gonadal sex hormones have been proposed to mediate the sex differences in food anticipatory activity (FAA) in rodents [46]. Recent studies have observed sex differences in FAA, but in a follow-up there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA [46]. Clearly more research is warranted into this highly complex area.…”

Food anticipatory activity on a calorie-restricted diet is independent of Sirt1

“…Finally, Satoh observed stronger effects of Sirt1 deletion in males than in females. While sex differences in FAA are documented, they are subtle [ 39 – 42 ]. As we used both male and female mice in our studies and observed robust inductions of FAA in all groups, where redistribution of activity to precede scheduled meals often exceeded 20% of total activity, we do not support sex differences as an explanation for the discrepancies between our results.…”

Studying food entrainment: Models, methods, and musings

“…However, a series of follow-up experiments opposes this finding that differences in FAA are related to gonadal sex hormone differences. Instead, Aguayo et al showed that singular manipulations to gonadal hormones, sex chromosomes, and developmental patterning in WT mice are not enough to explain the sex differences ( 75 ). This study used gonadectomized mice, sex chromosome copy mutants, and masculinized female mice that were treated with 17-β estradiol during their neonatal period and still reported no differences between males and females while on a calorie-restricted feeding paradigm ( 75 ).…”

“…Instead, Aguayo et al showed that singular manipulations to gonadal hormones, sex chromosomes, and developmental patterning in WT mice are not enough to explain the sex differences ( 75 ). This study used gonadectomized mice, sex chromosome copy mutants, and masculinized female mice that were treated with 17-β estradiol during their neonatal period and still reported no differences between males and females while on a calorie-restricted feeding paradigm ( 75 ). Therefore, while there are reports that indicate male mice to be generally more active than females, gonadal hormone differences alone cannot account for these findings.…”