Document Detail


Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro.
MedLine Citation:
PMID:  17033839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS/HYPOTHESIS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS/INTERPRETATION: SCD1 protects from cellular toxicity in L6 myotubes by preventing excessive accumulation of bioactive lipid metabolites.
Authors:
S K Pinnamaneni; R J Southgate; M A Febbraio; M J Watt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-11
Journal Detail:
Title:  Diabetologia     Volume:  49     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-10     Completed Date:  2007-09-18     Revised Date:  2012-05-24    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3027-37     Citation Subset:  IM    
Affiliation:
Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, RMIT University, Melbourne, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/RNA, Small Interfering; 154-17-6/Deoxyglucose; EC 1.14.19.1/Scd1 protein, mouse; EC 1.14.19.1/Stearoyl-CoA Desaturase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections
Erratum In:
Diabetologia. 2010 Jan;53(1):219

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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