RRC ID 36684
Author Sugimoto M, Shimizu Y, Zhao S, Ukon N, Nishijima K, Wakabayashi M, Yoshioka T, Higashino K, Numata Y, Okuda T, Tamaki N, Hanamatsu H, Igarashi Y, Kuge Y.
Title Characterization of the role of sphingomyelin synthase 2 in glucose metabolism in whole-body and peripheral tissues in mice.
Journal Biochim Biophys Acta
Abstract Sphingomyelin synthase 2 (SMS2) is a proposed potential therapeutic target for obesity and insulin resistance. However, the contributions of SMS2 to glucose metabolism in tissues and its possible therapeutic mechanisms remain unclear. Thus, to determine whole-body glucose utilization and the contributions of each insulin-targeted tissue to glucose uptake, we performed a glucose kinetics study, using the radiolabeled glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG), in wild-type (WT) and SMS2 knockout (KO) mice. Insulin signaling was enhanced in the liver, white adipose tissue and skeletal muscle of SMS2 KO mice compared with those of WT mice. In addition, compared with in WT mice, blood clearance of (18)F-FDG was accelerated in SMS2 KO mice when they were fed either a normal or a high fat diet. (18)F-FDG uptake was also increased in insulin-targeted tissues such as skeletal muscle in the SMS2 KO mice. Whereas skeletal muscle sphingolipid content was not clearly affected, plasma levels of very long-chain fatty acid (VLCFA)-containing ceramides were markedly increased in SMS2 KO mice, compared with in WT mice. We also generated liver-conditional SMS2 KO mice and performed glucose and insulin tolerance tests on mice with a high fat diet. However, no significant effect was observed. Thus, our study provided evidence that genetic inhibition of SMS2 elevated glucose clearance through activation of glucose uptake into insulin-targeted tissues such as skeletal muscle by a mechanism independent of hepatic SMS2. Our findings further indicate that this occurs, at least in part, via indirect mechanisms such as elevation of VLCFA-containing ceramides.
Volume 1861(8 Pt A)
Pages 688-702
Published 2016-8-1
DOI 10.1016/j.bbalip.2016.04.019
PII S1388-1981(16)30115-9
PMID 27151272
MeSH Adipose Tissue, White / enzymology* Animals Dietary Fats / pharmacology Glucose / genetics Glucose / metabolism* Insulin Resistance* Liver / enzymology* Mice Mice, Knockout Muscle, Skeletal / enzymology* Organ Specificity Transferases (Other Substituted Phosphate Groups) / genetics Transferases (Other Substituted Phosphate Groups) / metabolism*
IF 3.411
Times Cited 18
Mice RBRC01834