Cawthorn, William; Thomas, Benjamin; Suchacki, Karla. (2022). Cawthorn Lab: Data for sex differences manuscript, [dataset]. University of Edinburgh. Centre for Cardiovascular Science. https://doi.org/10.7488/ds/3277.
Source data for figures included in our manuscript about age-dependent sex differences in the metabolic effects of caloric restriction (version date 12 January 2022). The abstract is as follows:
"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; however, many aspects of the CR response remain poorly understood. In particular, sex differences in metabolic function are increasingly well recognised, yet 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, 30% CR decreased fat mass and fasting blood glucose and improved 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, while positron emission tomography-computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) 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 in 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, these studies 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."
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