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PMID: 17033839 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro.

Diabetologia ·Vol. 49 ·No. 12 ·2006-12-00 ·Pages 3027-37

Pinnamaneni SK, Southgate RJ, Febbraio MA, Watt MJ

Abstract

Stearoyl CoA desaturase 1 (SCD1) is implicated in mediating obesity and insulin resistance. Paradoxically, SCD1 converts saturated fatty acids, the lipid species implicated in mediating insulin resistance, to monounsaturated fatty acids. The aim of the present study was to assess the molecular mechanisms that implicate SCD1 in the aetiology of fatty acid-induced insulin resistance. SCD1 protein was transiently decreased or increased in rat L6 skeletal muscle myotubes using SCD1 short interfering RNA (siRNA) or liposome-mediated transfection of pcDNA3.1/Hygro-mSCD1, respectively. Reducing SCD1 protein resulted in marked esterification of exogenous fatty acids into diacylglycerol (DAG) and ceramide. Insulin-stimulated Akt activity and phosphorylation and 2-deoxyglucose uptake were reduced with SCD1 siRNA. Exposure of L6 myotubes to palmitate abolished insulin-stimulated glucose uptake in both control and SCD1 siRNA myotubes. Overexpression of SCD1 resulted in triacylglycerol esterification but attenuated ceramide and DAG accumulation and protected myotubes from fatty acid-induced insulin resistance. SCD1 protects from cellular toxicity in L6 myotubes by preventing excessive accumulation of bioactive lipid metabolites.

MeSH Terms
Animals Deoxyglucose/metabolism Fatty Acids/physiology Gene Expression Regulation, Enzymologic Insulin Resistance Male Mice Mice, Inbred C57BL Muscle Fibers, Skeletal/enzymology Muscle, Skeletal/enzymology,physiopathology Obesity/enzymology Proto-Oncogene Proteins c-akt/metabolism RNA, Small Interfering/genetics Stearoyl-CoA Desaturase/genetics,metabolism Transfection
Chemicals
Fatty Acids RNA, Small Interfering Deoxyglucose Scd1 protein, mouse Stearoyl-CoA Desaturase Proto-Oncogene Proteins c-akt
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pinnamaneni S K
Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, RMIT University, Melbourne, Victoria, Australia.
Southgate R J
Febbraio M A
Watt M J
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/s00125-006-0427-9
Published
2006-12-00
Epub
2006-00-11
Pages
3027-37
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1007/s00125-006-0427-9 View journal details
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