TY - GEN
T1 - The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent
AU - Thomas, Benjamin
AU - Suckacki, Karla
AU - Fyfe, Claire
AU - Tavares, Adriana A. S.
AU - Sulston, Richard
AU - Lovdel, Andrea
AU - Woodward, Holly
AU - Han, Xuan
AU - Mattiucci , Domenico
AU - Brain , Eleanor
AU - Alcaide-Corral, Carlos
AU - Gray, Gillian
AU - Whitfield, Phillip
AU - Stimson, Roland H.
AU - Morton, Nicholas M.
AU - Johnstone, Alexandra
AU - Cawthorn, William P
PY - 2021/11
Y1 - 2021/11
N2 - Caloric restriction (CR) is a nutritional intervention that reduces the risk of age-related diseases in numerous species, including humans. CR’s metabolic effects, including decreased fat mass and improved insulin sensitivity, play an important role in its broader health benefits, yet many aspects of the CR response remain poorly understood. In particular, sex differences in metabolic function are increasingly well recognised, but the extent and basis of sex differences in CR’s health benefits have been largely ignored. Herein, we addressed this gap in knowledge. In young (3-month-old) male mice, CR decreased fat mass and fasting blood glucose and improved both glucose tolerance and insulin sensitivity; however, in young female mice these effects were blunted or absent. Indirect calorimetry revealed that females’ resistance to fat and weight loss is not explained by decreased energy expenditure, positron emission tomography-computed tomography with 18F-fluorodeoxyglucose showed that altered peripheral glucose uptake does not account for the sex differences in glucose tolerance. Instead, the latter is associated with altered hepatic function, with CR decreasing gluconeogenesis and altering liver ceramide content in males but not females. To determine if oestrogen contributes to these sex differences, we next investigated the metabolic effects of CR initiated in aged mice (18-months old), when females are anoestrus. Strikingly, in these aged mice CR decreased fat mass and improved glucose homeostasis to a similar extent in both sexes. Finally, we found that CR-induced fat loss in humans is also sex- and age-dependent, with younger females resisting fat loss compared to younger males. Collectively, we identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR’s metabolic benefits. This has important implications for understanding the interplay between diet and health, and for maximising the benefits of CR in humans.
AB - Caloric restriction (CR) is a nutritional intervention that reduces the risk of age-related diseases in numerous species, including humans. CR’s metabolic effects, including decreased fat mass and improved insulin sensitivity, play an important role in its broader health benefits, yet many aspects of the CR response remain poorly understood. In particular, sex differences in metabolic function are increasingly well recognised, but the extent and basis of sex differences in CR’s health benefits have been largely ignored. Herein, we addressed this gap in knowledge. In young (3-month-old) male mice, CR decreased fat mass and fasting blood glucose and improved both glucose tolerance and insulin sensitivity; however, in young female mice these effects were blunted or absent. Indirect calorimetry revealed that females’ resistance to fat and weight loss is not explained by decreased energy expenditure, positron emission tomography-computed tomography with 18F-fluorodeoxyglucose showed that altered peripheral glucose uptake does not account for the sex differences in glucose tolerance. Instead, the latter is associated with altered hepatic function, with CR decreasing gluconeogenesis and altering liver ceramide content in males but not females. To determine if oestrogen contributes to these sex differences, we next investigated the metabolic effects of CR initiated in aged mice (18-months old), when females are anoestrus. Strikingly, in these aged mice CR decreased fat mass and improved glucose homeostasis to a similar extent in both sexes. Finally, we found that CR-induced fat loss in humans is also sex- and age-dependent, with younger females resisting fat loss compared to younger males. Collectively, we identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR’s metabolic benefits. This has important implications for understanding the interplay between diet and health, and for maximising the benefits of CR in humans.
UR - https://www.endocrine-abstracts.org/ea/0077/ea0077P171
U2 - 10.1530/endoabs.77.P171
DO - 10.1530/endoabs.77.P171
M3 - Published conference contribution
T3 - Endocrine Abstracts
BT - Society for Endocrinology BES 2021
PB - BioScientifica
T2 - Society for Endocrinology BES 2021
Y2 - 8 November 2021 through 10 November 2021
ER -