Document Detail


Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity.
MedLine Citation:
PMID:  16436371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Triglyceride synthesis in most mammalian tissues involves the sequential addition of fatty acids to a glycerol backbone, with unique enzymes required to catalyze each acylation step. Acylation at the sn-2 position requires 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) activity. To date, seven Agpat genes have been identified based on activity and/or sequence similarity, but their physiological functions have not been well established. We have generated a mouse model deficient in AGPAT6, which is normally expressed at high levels in brown adipose tissue (BAT), white adipose tissue (WAT), and liver. Agpat6-deficient mice exhibit a 25% reduction in body weight and resistance to both diet-induced and genetically induced obesity. The reduced body weight is associated with increased energy expenditure, reduced triglyceride accumulation in BAT and WAT, reduced white adipocyte size, and lack of adipose tissue in the subdermal region. In addition, the fatty acid composition of triacylglycerol, diacylglycerol, and phospholipid is altered, with proportionally greater polyunsaturated fatty acids at the expense of monounsaturated fatty acids. Thus, Agpat6 plays a unique role in determining triglyceride content and composition in adipose tissue and liver that cannot be compensated by other members of the Agpat family.
Authors:
Laurent Vergnes; Anne P Beigneux; Ryan Davis; Steven M Watkins; Stephen G Young; Karen Reue
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-01-25
Journal Detail:
Title:  Journal of lipid research     Volume:  47     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-24     Completed Date:  2006-10-05     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  745-54     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
1-Acylglycerol-3-Phosphate O-Acyltransferase / genetics,  metabolism*
Adipose Tissue / cytology,  metabolism
Animals
Body Weight
Energy Metabolism
Female
Gene Expression Regulation
Isoenzymes / genetics,  metabolism
Lipids / chemistry
Lipodystrophy / genetics,  metabolism*
Male
Mice
Mice, Knockout
Obesity*
Skin / cytology,  metabolism,  pathology
Thermogenesis
Grant Support
ID/Acronym/Agency:
R01 HL094732/HL/NHLBI NIH HHS; R01 HL094732-01/HL/NHLBI NIH HHS; R01 HL094732-01S1/HL/NHLBI NIH HHS; R01 HL094732-02/HL/NHLBI NIH HHS; R01 HL094732-03/HL/NHLBI NIH HHS; U01 HL-66621/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Lipids; EC 2.3.1.51/1-Acylglycerol-3-Phosphate O-Acyltransferase
Comments/Corrections

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