Document Detail

Loss of Ncb5or results in impaired fatty acid desaturation, lipoatrophy, and diabetes.
MedLine Citation:
PMID:  18682384     Owner:  NLM     Status:  MEDLINE    
Targeted ablation of the novel flavoheme reductase Ncb5or knock-out (KO) results in progressive loss of pancreatic beta-cells and white adipose tissue over time. Lipoatrophy persisted in KO animals in which the confounding metabolic effects of diabetes were eliminated by islet transplantation (transplanted knockout (TKO)). Lipid profiles in livers prepared from TKO animals were markedly deficient in triglycerides and diacylglycerides. Despite enhanced expression of stearoyl-Co-A desaturase-1, levels of palmitoleic and oleic acids (Delta9 fatty acid desaturation) were decreased in TKO relative to wild type controls. Treatment of KO hepatocytes with palmitic acid reduced cell viability and increased apoptosis, a response blunted by co-incubation with oleic acid. The results presented here support the hypothesis that Ncb5or supplies electrons for fatty acid desaturation, offer new insight into the regulation of a crucial step in fatty acid biosynthesis, and provide a plausible explanation for both the diabetic and the lipoatrophic phenotype in Ncb5or(-/-) mice.
Kevin Larade; Zhigang Jiang; Yongzhao Zhang; WenFang Wang; Susan Bonner-Weir; Hao Zhu; H Franklin Bunn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-05
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-20     Completed Date:  2008-12-11     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29285-91     Citation Subset:  IM    
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Cell Survival
Cytochrome-B(5) Reductase / metabolism*
Diabetes Mellitus, Experimental / metabolism*
Fatty Acids / metabolism*
Fatty Acids, Monounsaturated / metabolism
Hepatocytes / metabolism
Islets of Langerhans Transplantation
Lipids / chemistry
Mice, Knockout
Models, Biological
Oleic Acid / chemistry,  metabolism
Palmitic Acid / metabolism
Grant Support
Reg. No./Substance:
0/Fatty Acids; 0/Fatty Acids, Monounsaturated; 0/Lipids; 112-80-1/Oleic Acid; 209B6YPZ4I/palmitoleic acid; 57-10-3/Palmitic Acid; EC 1.6.2.-/Ncb5or protein, mouse; EC Reductase

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