The Role of Sphingolipid Metabolism in Endocrine Diseases

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Background

The role of sphingolipids in endocrine diseases

Sphingolipids, a major class of lipids including sphingosine, sphingosine-1-phosphate, ceramide, sphingomyelin, glucosylceramide, etc., are composed of a long fatty acid chain and a polar head group in position one. Ceramide is the central core serving as backbone for biosynthesis and metabolism of sphingolipids. Sphingolipids were recognized as structural components of cell membrane molecules in beginning. In recent decades, these bioactive lipids are further known playing critical roles in regulating physiological and pathophysiological functions. Interestingly, various diseases have an alteration of sphingolipid catabolic enzymes, such as sphingosine kinases, ceramidases, and sphingomyelinase, which are responsible for generating multiple sphingolipids.

Endocrine diseases are major causes of immature illness and death, which imposes a substantial financial burden to the society. Emerging evidences have shown that these diseases are often associated with change of sphingolipids metabolism and related key enzymes. For instance, the altering of plasma sphingolipids profiling and the increasing of ceramide concentrations may contribute to impaired glucose homeostasis, insulin resistance, and increased level of triglyceride-rich lipoproteins. In addition, emerging studies over the years have highlighted the importance of sphingolipids in human endocrine diseases, including but not limited to type 2 diabetes, steatosis, cholesterol homeostasis, pituitary diseases, and thyroid disorders.

Considering the critical role of sphingolipids in multiple cellular biological responses and cell signalling cascades, the consequences for imbalance of sphingolipids might be substantial in development of host diseases. Although there have been significant advances in studying therapeutic roles of sphingolipids and key enzymes in endocrine diseases, the precise mechanisms is still far to be understood.

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, obesity, steatosis pituitary diseases, and thyroid disorders. 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 endocrine diseases 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 beta-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 sphingolipid in the regulation of pituitary diseases;

• Role of sphingolipid in the regulation of thyroid disorders;

• Role of atypical sphingolipid in the regulation of glucose homeostasis.

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Keywords: Sphingolipid; Diabetes; Obesity; Lipidomics; glucose homeostasis

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