First Author | Turpin SM | Year | 2014 |
Journal | Cell Metab | Volume | 20 |
Issue | 4 | Pages | 678-86 |
PubMed ID | 25295788 | Mgi Jnum | J:215519 |
Mgi Id | MGI:5605583 | Doi | 10.1016/j.cmet.2014.08.002 |
Citation | Turpin SM, et al. (2014) Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metab 20(4):678-86 |
abstractText | Ceramides increase during obesity and promote insulin resistance. Ceramides vary in acyl-chain lengths from C14:0 to C30:0 and are synthesized by six ceramide synthase enzymes (CerS1-6). It remains unresolved whether obesity-associated alterations of specific CerSs and their defined acyl-chain length ceramides contribute to the manifestation of metabolic diseases. Here we reveal that CERS6 mRNA expression and C16:0 ceramides are elevated in adipose tissue of obese humans, and increased CERS6 expression correlates with insulin resistance. Conversely, CerS6-deficient (CerS6(Delta/Delta)) mice exhibit reduced C16:0 ceramides and are protected from high-fat-diet-induced obesity and glucose intolerance. CerS6 deletion increases energy expenditure and improves glucose tolerance, not only in CerS6(Delta/Delta) mice, but also in brown adipose tissue- (CerS6(DeltaBAT)) and liver-specific (CerS6(DeltaLIVER)) CerS6 knockout mice. CerS6 deficiency increases lipid utilization in BAT and liver. These experiments highlight CerS6 inhibition as a specific approach for the treatment of obesity and type 2 diabetes mellitus, circumventing the side effects of global ceramide synthesis inhibition. |