Sex differences in intraorgan fat levels and hepatic lipid metabolism: implications for cardiovascular health and remission of type 2 diabetes after dietary weight loss – published online 16/10/2021

Aaron Jesuthasan, Sviatlana Zhyzhneuskaya, Carl Peters, Alison C. Barnes, Kieren G. Hollingsworth, Naveed Sattar, Michael E. J. Lean, Roy Taylor, Ahmad H. Al-Mrabeh

The cardiovascular risks associated with type 2 diabetes are increased to a greater extent in women compared with men. The metabolic basis for this sex difference is not known. In this issue, Jesuthasan et al (https://doi.org/10.1007/s00125-021-05583-4) report that women without diabetes have lower levels of triacylglycerol in their liver compared with men, but this difference is lost in individuals with diabetes. The authors also report levels of plasma insulin, a driver of hepatic de novo lipogenesis, which are normally lower in women than men, were as high in women with diabetes as in men with diabetes. Higher levels of fat in the liver leads to higher rates of VLDL secretion. As the most atherogenic lipid particles (small dense LDL) are derived from VLDL particles after release of triacylglycerol, the authors propose that the relatively greater cardiovascular risk in women is directly linked to the greater increase in intrahepatic fat during type 2 diabetes. The authors conclude that management of type 2 diabetes by substantial weight loss is particularly important for cardiovascular health in women.

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