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

J Lipid Res. 2012 Jun;53(6):1071-9. doi: 10.1194/jlr.M022160. Epub 2012 Apr 6.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D
  • ATP-Binding Cassette Transporters / metabolism*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Dietary Fats / adverse effects*
  • Disease Susceptibility
  • Dyslipidemias / chemically induced
  • Dyslipidemias / metabolism
  • Erucic Acids / adverse effects*
  • Fatty Liver / chemically induced
  • Fatty Liver / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Insulin Resistance
  • Lipid Metabolism / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / chemically induced
  • Obesity / metabolism

Substances

  • ABCD2 protein, mouse
  • ATP Binding Cassette Transporter, Subfamily D
  • ATP-Binding Cassette Transporters
  • Blood Glucose
  • Dietary Fats
  • Erucic Acids
  • erucic acid