title: The absence of ABCD2 sensitizes mice to disruptions in lipid metabolism by dietary erucic acid.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Brown
authors.forename: Kylie E
authors.initials: KE
authors.lastname: Newman
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Saloni
authors.initials: S
authors.lastname: Bhatnagar
authors.forename: Xiangan
authors.initials: X
authors.lastname: Li
authors.forename: Aurora
authors.initials: A
authors.lastname: Pujol
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Graf
mesh_terms: D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects*; D004198:Disease Susceptibility; D050171:Dyslipidemias / Q000139:chemically induced / Q000378:metabolism; D004883:Erucic Acids / Q000009:adverse effects*; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism
chemical_list: C508354:ABCD2 protein, mouse; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D004041:Dietary Fats; D004883:Erucic Acids; C049811:erucic acid