PerspectiveMetabolism

Lowering ceramides to overcome diabetes

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Science  26 Jul 2019:
Vol. 365, Issue 6451, pp. 319-320
DOI: 10.1126/science.aax6594

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Summary

Excess nutrient intake leads to a disruption in metabolic homeostasis. In particular, prolonged periods of excess glucose intake can directly contribute to deterioration of insulin sensitivity. Insulin is a key player in the disposal of carbohydrates from food. Frequently associated with this insulin resistance is a dysregulation of lipid metabolism that can lead to lipotoxicity, whereby excess lipids wreak havoc on important intracellular signaling pathways. However, it is largely unknown what types of lipids trigger these cytotoxic effects, which result in further deterioration of glucose and lipid homeostasis. Concentrations of ceramide lipids in blood plasma and tissues are strongly associated with the risk of developing type 2 diabetes (T2D), hepatic steatosis, and cardiovascular disease, which are caused by lipotoxicity and insulin resistance (1, 2). On page 386 of this issue, Chaurasia et al. (3) provide evidence that therapeutically intervening in the ceramide biosynthesis pathway in mice can improve metabolic homeostasis.

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