 Calorie restriction, CR, reduces the risk of age-related diseases in numerous species, including humans. It has been shown to reduce fat mass and improve glucose tolerance and insulin sensitivity in young males, but this effect is blunted or absent in young females. Furthermore, female resistance to fat loss is associated with decreased lipolysis, energy expenditure and fatty acid oxidation, and increased post-prandial lipogenesis, which is different from males. Additionally, females have lower TCA cycle activity and higher blood ketone concentrations which may be due to hepatic acetyl-CoA content being used for the TCA cycle instead of fatty acids. This suggests that males use hepatic acetyl-CoA for the TCA cycle, whereas in females it accumulates, stimulating gluconeogenesis and limiting hypoglycemia during CR. In aged mice, 18 months old, when females are inestrous, CR decreases fat mass and improves glucose homeostasis similarly in both sexes. In contrast, in overweight and obese humans, CR-induced fat loss is also sex and age. This article was authored by Carla Jasonciacchi, Benjamin J. Thomas, Yeshiko Emakushima and others. We are article.tv, links in the description below.