The adipokine Retnla modulates cholesterol homeostasis in hyperlipidemic mice

Mi Ran Lee, Chae Ji Lim, You Han Lee, Jong Gil Park, Seong Keun Sonn, Mi Ni Lee, In Hyuk Jung, Se Jin Jeong, Sejin Jeon, Myoungsook Lee, Ki Sook Oh, Young Yang, Jae Bum Kim, Hueng Sik Choi, Woojin Jeong, Tae Sook Jeong, Won Kee Yoon, Hyoung Chin Kim, Jae Hoon Choi, Goo Taeg Oh

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23 Scopus citations

Abstract

Hyperlipidemia is a well-recognized risk factor for atherosclerosis and can be regulated by adipokines. Expression of the adipokine resistin-like molecule alpha (Retnla) is regulated by food intake; whether Retnla has a role in the pathogenesis of hyperlipidemia and atherosclerosis is unknown. Here we report that Retnla has a cholesterol-lowering effect and protects against atherosclerosis in low-density lipoprotein receptor-deficient mice. On a high-fat diet, Retnla deficiency promotes hypercholesterolaemia and atherosclerosis, whereas Retnla overexpression reverses these effects and improves the serum lipoprotein profile, with decreased cholesterol in the very low-density lipoprotein fraction concomitant with reduced serum apolipoprotein B levels. We show that Retnla upregulates cholesterol-7-α -hydroxylase, a key hepatic enzyme in the cholesterol catabolic pathway, through induction of its transcriptional activator liver receptor homologue-1, leading to increased excretion of cholesterol in the form of bile acids. These findings define Retnla as a novel therapeutic target for treating hypercholesterolaemia and atherosclerosis.

Original languageEnglish
Article number4410
JournalNature Communications
Volume5
DOIs
StatePublished - 15 Jul 2014

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