In many developed and developing countries, type 2 diabetes (T2D) is one of the major causes of immature illness and death, which imposes a substantial financial burden to the society. T2D is associated with defects observed in both insulin sensitivity and insulin secretion but also in pancreatic  cell apoptosis. During diabetes, the imbalanced regulation of glucose levels results in a chronic and abnormal elevation of plasma glucose levels that lead to heart disease, kidney failure, limb amputation, and blindness.

Evidence suggests that T2D is often associated with obesity. Indeed, persistent elevated levels of circulating free fatty acids (FFA) can lead to a saturation of the adipose tissue and to an ectopic storage of FFA in other peripheral tissues. Chronically elevated levels of FFAs cause peripheral insulin resistance and impairment of insulin secretion by pancreatic  cells. This phenomenon has been defined as ‘lipotoxicity’.

Among the lipids that accumulate in these tissues, sphingolipid such as ceramides have been shown to play a crucial role in mediating lipotoxicity. More recently, other sphingolipid metabolites such as glucosylceramide and sphingomyelin, but also sphingosine-1-phosphate, have been shown to play a central role either in the regulation of insulin resistance or the dysfunction of pancreatic  cells. The role of these sphingolipid metabolites in T2D has been drastically improved thanks to the cloning of gene encoding various enzymes involved in sphingolipid metabolism and the development of total and tissue-targeted knock-out of these gene mice models.

The scope of the Research Topic is therefore to cover promising, recent, and novel research trends in the role of enzyme regulating sphingolipid metabolites in the development of type 2 diabetes and obesity. This will also include the potential role of sphingolipid transporters and receptors able to facilitate or transduce the effect of sphingolipid. The ultimate goal is therefore to review the role of sphingolipid metabolism (of ceramide, glucosylceramide, S1P but also atypical sphingolipid such as deoxysphingolipid) in the development of T2D linked to obesity through the analysis of the function of their metabolizing enzyme (in cellulo and in vivo). Areas to be covered in this Research Topic may include, but are not limited to:
• Regulation of peripheral insulin sensitivities and secretion by sphingolipid metabolism
• Regulation of pancreatic  cell apoptosis and differentiation by sphingolipid metabolism
• Regulation of thermogenesis by BAT and beiging of adipose tissue by sphingolipid metabolism
• Regulation of steatosis through lipid metabolism and inflammation by sphingolipid metabolism
• Regulation of brain insulin signaling and its repercussion on glucose homeostasis by sphingolipid metabolism
• Role of sphingolipid receptor and transporter in the regulation of glucose homeostasis
• Role of atypical sphingolipid in the regulation of glucose homeostasis

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Frontiers in Endocrinology

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