Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA.
J Lipid Res. 2012 Jun;53(6):1071-9. doi: 10.1194/jlr.M022160. Epub 2012 Apr 6.
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.
ABCD2（D2）是一种过氧化物酶体转运蛋白，在脂肪组织中含量丰富，可促进长链 MUFA 的氧化。芥酸（EA，22:1ω9）可减少 X 连锁肾上腺脑白质营养不良患者的极长链饱和脂肪酸，但可促进大鼠的血脂异常和扩张型心肌病。为了确定 D2 在 EA 代谢中的作用，我们用富含 EA 的饮食挑战了野生型和 D2 缺乏型（D2 KO）小鼠。在 D2 KO 小鼠中，饮食 EA 导致脂肪组织迅速扩张、脂肪细胞肥大、肝脂肪变性和血糖控制丧失。然而，D2 对两种饮食诱导肥胖模型中肥胖表型的发展没有影响。尽管 D2 KO 小鼠肝脏中的 EA 显著增加，但它不到所有脂肪酸的 2%。EA 的代谢产物（20:1、18:1 和 16:1）升高，特别是 18:1，占所有脂肪酸的 50%。这些数据表明，脂肪组织中 EA 代谢失败导致肝脏中 EA 代谢、脂肪酸谱紊乱以及肥胖的发展，并揭示了 D2 在保护机体免受饮食 EA 方面的重要作用。
