Sphingolipids in obesity and related complications

Abstract

Sphingolipids are biologically active lipids ubiquitously produced in all vertebrate cells. Asides from structural components of cell membrane, sphingolipids also function as intracellular and extracellular mediators that regulate many important physiological cellular processes including cell survival, proliferation, apoptosis, differentiation, migration and immune processes. Recent studies have also indicated that disruption of sphingolipid metabolism is strongly associated with different diseases that exhibit diverse neurological and metabolic consequences. Here, we briefly summarize current evidence for understanding of sphingolipid pathways in obesity and associated complications. The regulation of sphingolipids and their enzymes may have a great impact in the development of novel therapeutic modalities for a variety of metabolic diseases.

Figure 1

Sphingolipid biosynthetic pathways. Inhibition of indicated biosynthetic enzymes is associated with prevention of chronic metabolic diseases. SPT: Serine Palmotoyl transferase; DES1, Dihydroceramide saturase 1; SMS: Sphingomyelinase synthase; GCS: Glucosylceramide synthase; SK: Sphingosine kinase; Cdase: Cearmidase.

Figure 2

Elevated ceramide and sphiomyelin in obese adipocytes elicit the pathophysiological events in various tissues and organs. CVD: Cardiovascular disease.

Figure 3

Plasma total ceramide concentrations, delta body weight, glomerular injury in C57BL/6J mice on low fat or high fat diet with or without amitriptyline treatment. Data are arithmetic means ± SE (n=4-12 each group) of plasma total ceramide concentrations (A), delta body weight (B), Photomicrographs show typical glomerular structure (original magnification, ×400) in LFD or HFD treatment with or without amitriptyline treatment (C) Summarized data of glomerular damage index (GDI) by semi-quantitation of scores in 4 different groups of mice (n=6 each group). For each kidney section, 50 glomeruli were randomly chosen for the calculation of GDI in LFD or HFD fed C57BL/6J mice with or without amitriptyline treatment (D). * Significant difference (P<0.0.5) compared to the values from mice receiving the LFD, # Significant difference (P<0.0.5) compared to the values from mice receiving the HFD. Scale bar represents 50 μm.

Figure 4

Diagram of visfatin-induced membrane raft clustering that results in the formation of membrane raft redox signaling platforms in coronary artery endothelial cells.