Gonadal hormones influence core body temperature during calorie restriction

Abstract

During calorie restriction (CR), endotherms adjust several physiological processes including the decrease of core body temperature (T b ) and reduction of energy expenditure. We recently found that CR-induced hypothermia is regulated in a sex-dependent manner in mice with lowered central insulin-like growth factor receptor signaling. Here, we describe the contribution of sex hormones to CR-induced hypothermia in wild type C57BL6 mice by measuring T b of female and male mice following bilateral gonadectomy and hormonal replacement. Specifically, we evaluated the effects of progesterone (P4), 17-ß estradiol (E2), a combination of both (P4 + E2) in females and of 5-α dihydrotestosterone (5-α DHT) in males. Gonadectomy resulted in an earlier and stronger CR-induced hypothermia in both sexes. These effects were fully antagonized in females by E2 replacement, but not by P4, which had only minor and partial effects when used alone and did not prevent the action of E2 during CR when both hormones were given in combination. 5-α-DHT had only minor and transient effects on preventing the reduction of T b during CR on gonadectomized male mice. These findings indicate that gonadal hormones contribute to sex-specific regulation of T b and energy expenditure when nutrient availability is scarce.

The feeding microstructure of male and female mice

“…In connection with that and within the limitations of our experiments imposed by the comparatively small number of male and female mice (n = 10) used, our results suggest that acutely eliminating �70% of mice' net daily energy intake resulted in ~5-7% BW loss (Fig 3A -3C), as noted in previous studies using single-housed C57BL/6J mice [77]. Although these data suggest that a similar caloric restriction reduces metabolic rate or net energy expenditure to a similar extent in social males and females, fasting-induced hypothermia was significantly more pronounced in 10-20w old females (S4A Fig), as previously reported for single-caged mice [86,87]. Since fat mass contributes to whole-body metabolism by regulating thermogenic activity [88] and males housed in groups showed increased fat mass, our results suggest that the thermoregulatory mechanisms involved in heat production/ loss is sex-and age-dependent in house grouped mice.…”

Testosterone reduces metabolic brown fat activity in male mice

“…While we show that increased metabolic BAT activity following castration could be reversed with testosterone replacement, we have not performed similar studies addressing body temperature. In a recent study, DHT treatment reduced core body temperature in castrated male mice during the inactive period of the day (Cintron-Colon et al 2019), supporting AR-mediated effects of androgens on body temperature. To our knowledge, there are no studies addressing whether men with low testosterone levels due to endocrine disorders or treatments have increased body temperature; simple association studies between these variables will likely be confounded by disorders such as obesity (Kahn & Brannigan 2017).…”

Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss

“…Figures 2 and 4A-4C, animals were on a 50% CR regimen and treatments were started once the daily hypothermic response [80] (T b < 34 C for approximately 6-8 hours) was consistently established, 14 days after the CR protocol was started. Food was provided daily, during a one-hour window before the lights were turned off (ZT12).…”