The adipokine Retnla modulates cholesterol homeostasis in hyperlipidemic mice
- Title
- The adipokine Retnla modulates cholesterol homeostasis in hyperlipidemic mice
- Author
- 최재훈
- Keywords
- RESISTIN-LIKE-MOLECULE; BILE-ACID SYNTHESIS; INDUCED INSULIN-RESISTANCE; E-DEFICIENT MICE; ADIPOSE-TISSUE; TYPE-2 INFLAMMATION; PROMOTES ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; TRANSGENIC EXPRESSION; NUCLEAR RECEPTORS
- Issue Date
- 2014-07
- Publisher
- Nature Publishing Group
- Citation
- Nature Communications, 6, P.1-13
- 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.
- URI
- https://www.nature.com/articles/ncomms7076
- ISSN
- 2041-1723
- DOI
- 10.1038/ncomms7076
- Appears in Collections:
- COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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