Sphingolipids in adipose tissue: What's tipping the scale?

Abstract

Adipose tissue lies at the heart of obesity, mediating its many effects upon the rest of the body, with its unique capacity to expand and regenerate, throughout the lifespan of the organism. Adipose is appreciated as an endocrine organ, with its myriad adipokines that elicit both physiological and pathological outcomes. Sphingolipids, bioactive signaling molecules, affect many aspects of obesity and the metabolic syndrome. While sphingolipids are appreciated in the context of these diseases in other tissues, there are many discoveries yet to be uncovered in the adipose tissue. This review focuses on the effects of sphingolipids on various aspects of adipose function and dysfunction. The processes of adipogenesis, metabolism and thermogenesis, in addition to inflammation and insulin resistance are intimately linked to sphingolipids as discussed below.

Keywords: Adipogenesis; Inflammation; Insulin resistance; Obesity; Sphingolipid synthesis.

Fig. 1.

Sphingolipid biosynthetic pathway.

Fig. 2.

Healthy (top) vs. unhealthy (bottom) adipose tissue. Healthy adipose tissue requires functional insulin signaling, adipogenesis, and lipid storage. It is marked by balanced production of sphingolipids, high adiponectin production and release of anti-inflammatory cytokines from resident M2 macrophages. In the pathological state, elevated levels of sphingolipids are released, in addition to excess free fatty acids (FFAs), and proinflammatory cytokines from M1 macrophages. GM3 interferes with insulin receptor localization to caveolae, while elevated ceramides and proinflammatory cytokines interfere with downstream aspects of insulin signaling. Aberrant sphingolipid synthesis, inflammation, and excess FFAs also interfere with adipogenesis and lipogenesis.