Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.

Sphingolipids, a class of lipids, are widely present in the cell membranes of all eukaryotic and some prokaryotic organisms. These lipids play crucial roles in the formation of the lipid bilayer and are categorised into several groups, including sphingomyelins, ceramides, sphingosine-1-phosphate, and glycosphingolipids. In addition to their structural significance, sphingolipids also show bioactivity, regulating various signalling pathways involved in cell growth, differentiation, ageing, and apoptosis, and are closely associated with several chronic diseases, including obesity and type 2 diabetes mellitus. Notably, dysregulated sphingolipid metabolism contributes to obesity-related metabolic dysfunction through altered lipid accumulation, insulin signalling, organelle stress, and inflammation. This review summarises the various mechanisms and recent research advances related to sphingolipids and their association with obesity. It further examines how the metabolic effects of ceramides vary according to their acyl-chain length, enzyme of origin, tissue distribution, and metabolic context, as well as how adipose depot, sex, age, and metabolic phenotype influence the sphingolipid response to obesity. It further considers plant-derived sphingolipids as a compositionally distinct exogenous input to host sphingolipid pools, comparing their structural and enzymatic features with those of mammalian sphingolipids. Pharmacological, dietary, and lifestyle approaches that modify sphingolipid metabolism are also considered. Accordingly, the review summarises our current knowledge regarding the dietary occurrence, intestinal handling, and metabolic effects of sphingolipids and identifies the evidence gaps that currently limit conclusions regarding their relevance to obesity.