Document Detail

The absence of ABCD2 sensitizes mice to disruptions in lipid metabolism by dietary erucic acid.
MedLine Citation:
PMID:  22493092     Owner:  NLM     Status:  MEDLINE    
ABCD2 (D2) is a peroxisomal transporter that is highly abundant in adipose tissue and promotes the oxidation of long-chain MUFA. Erucic acid (EA, 22:1ω9) reduces very long chain saturated fatty acids in patients with X-linked adrenoleukodystrophy but promotes dyslipidemia and dilated cardiomyopathy in rats. To determine the role of D2 in the metabolism of EA, we challenged wild-type and D2 deficient mice (D2 KO) with an enriched EA diet. In D2 KO mice, dietary EA resulted in the rapid expansion of adipose tissue, adipocyte hypertrophy, hepatic steatosis, and the loss of glycemic control. However, D2 had no impact on the development of obesity phenotypes in two models of diet-induced obesity. Although there was a significant increase in EA in liver of D2 KO mice, it constituted less than 2% of all fatty acids. Metabolites of EA (20:1, 18:1, and 16:1) were elevated, particularly 18:1, which accounted for 50% of all fatty acids. These data indicate that the failure to metabolize EA in adipose results in hepatic metabolism of EA, disruption of the fatty acid profile, and the development of obesity and reveal an essential role for D2 in the protection from dietary EA.
Jingjing Liu; Shuang Liang; Xiaoxi Liu; J Andrew Brown; Kylie E Newman; Manjula Sunkara; Andrew J Morris; Saloni Bhatnagar; Xiangan Li; Aurora Pujol; Gregory A Graf
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-06
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-10     Completed Date:  2012-09-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1071-9     Citation Subset:  IM    
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA.
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MeSH Terms
ATP-Binding Cassette Transporters / metabolism*
Adipose Tissue / drug effects,  metabolism
Blood Glucose / metabolism
Dietary Fats / adverse effects*
Disease Susceptibility
Dyslipidemias / chemically induced,  metabolism
Erucic Acids / adverse effects*
Fatty Liver / chemically induced,  metabolism
Gene Expression Regulation / drug effects
Insulin Resistance
Lipid Metabolism / drug effects*
Mice, Inbred C57BL
Obesity / chemically induced,  metabolism
Grant Support
5P20RR021954-05/RR/NCRR NIH HHS; 8 P20 GM103527-05/GM/NIGMS NIH HHS; R01DK077632/DK/NIDDK NIH HHS; R01DK080874/DK/NIDDK NIH HHS; R01GM50388-19/GM/NIGMS NIH HHS
Reg. No./Substance:
0/ABCD2 protein, mouse; 0/Blood Glucose; 0/Dietary Fats; 0/Erucic Acids; 075441GMF2/erucic acid

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

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