The absence of ABCD2 sensitizes mice to disruptions in lipid metabolism by dietary erucic acid[S]

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...

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Bibliographic Details
Published in:	Journal of lipid research Vol. 53; no. 6; pp. 1071 - 1079
Main Authors:	Liu, Jingjing, Liang, Shuang, Liu, Xiaoxi, Brown, J.Andrew, Newman, Kylie E., Sunkara, Manjula, Morris, Andrew J., Bhatnagar, Saloni, Li, Xiangan, Pujol, Aurora, Graf, Gregory A.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-06-2012 The American Society for Biochemistry and Molecular Biology Elsevier
Subjects:	adipocyte adipose Adipose Tissue - drug effects Adipose Tissue - metabolism adrenoleukodystrophy Animals ATP Binding Cassette Transporter, Subfamily D ATP-Binding Cassette Transporters - metabolism Blood Glucose - metabolism Dietary Fats - adverse effects Disease Susceptibility Dyslipidemias - chemically induced Dyslipidemias - metabolism Erucic Acids - adverse effects fatty liver Fatty Liver - chemically induced Fatty Liver - metabolism Female Gene Expression Regulation - drug effects Insulin Resistance Lipid Metabolism - drug effects Lorenzo's Oil Mice Mice, Inbred C57BL Obesity - chemically induced Obesity - metabolism peroxisome Lorenzo's Oil adrenoleukodystrophy adipocyte peroxisome fatty liver adipose insulin resistance
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Summary:	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.
ISSN:	0022-2275 1539-7262
DOI:	10.1194/jlr.M022160