Sphingolipid Turnover Inhibitors as Modulators of Cellular Metabolism and Obesity

Sphingolipids are important structural components of cellular membranes which are involved in the regulation of cell growth and death. Sphingolipids metabolites have profound effects on energy production, nutrient utilization and cellular metabolism. Ceramide-induced metabolic impairments contribute to the tissue malfunction associated with obesity. Ceramides are the key intermediates in the biosynthesis of all complex sphingolipids, located in the membranes, where they participate in raft formation and are accumulated in the cells in response to the stress stimuli. Ceramide accumulation in blood serum, liver, adipose tissue, and muscle are associated with the obesity and metabolic disease. Sphingomyelin hydrolysis, de novo synthesis and the salvage pathway are three major pathways for ceramide production and the key enzymes of ceramide metabolism can be the useful targets for cellular lipid modulation. The inhibition of ceramide production results in reduced weight, prevented the diet-induced obesity and a variety of obesity-induced metabolic disorders, too. This chapter will be focused on the role of sphingolipid metabolites in the regulation of lipid storage in cells and tissues. Much attention will be given to the role of ceramide in lipogenesis deregulation. The metabolic benefits of sphingolipid turnover inhibition in obese rodents will be analyzed.

Keywords: Cellular metabolism regulation, ceramidase, ceramide synthase, ceramides, dihydroceramide desaturase, glucosylceramide synthase, inhibitors of sphingolipid turnover, obesity, serine palmitoyltransferase, sphingomyelinases.