Circulating Sphingolipids and Glucose Homeostasis: An Update

Abstract

Sphingolipids are a family of lipid molecules produced through different pathways in mammals. Sphingolipids are structural components of membranes, but in response to obesity, they are implicated in the regulation of various cellular processes, including inflammation, apoptosis, cell proliferation, autophagy, and insulin resistance which favors dysregulation of glucose metabolism. Of all sphingolipids, two species, ceramides and sphingosine-1-phosphate (S1P), are also found abundantly secreted into the bloodstream and associated with lipoproteins or extracellular vesicles. Plasma concentrations of these sphingolipids can be altered upon metabolic disorders and could serve as predictive biomarkers of these diseases. Recent important advances suggest that circulating sphingolipids not only serve as biomarkers but could also serve as mediators in the dysregulation of glucose homeostasis. In this review, advances of molecular mechanisms involved in the regulation of ceramides and S1P association to lipoproteins or extracellular vesicles and how they could alter glucose metabolism are discussed.

The impacts of dietary sphingomyelin supplementation on metabolic parameters of healthy adults: a systematic review and meta-analysis of randomized controlled trials

“…It has been demonstrated that LDL-Cer inhibits insulin signaling in muscle, while HDL-S1P improves insulin signaling and enhances the function and survival of pancreatic cells (77,81,82). HDL-S1P and LDL-Cer exhibit contrasting effects on the progression of T2DM (76). Hence, the process of interconversion among these sphingolipid species is subject to strict regulation.…”