Sphingolipid Turnover Inhibitors as Modulators of Cellular Metabolism and Obesity
Pp. 242-263 (22)
Nataliya A. Babenko
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.
Cellular metabolism regulation, ceramidase, ceramide synthase,
ceramides, dihydroceramide desaturase, glucosylceramide synthase, inhibitors of
sphingolipid turnover, obesity, serine palmitoyltransferase, sphingomyelinases.
Department of Physiology of Ontogenesis, Institute of Biology, Kharkov Karazin National University, 4 Svobody pl., 61077 Kharkov, Ukraine.