| First Author | Lee MR | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 4410 | PubMed ID | 25022542 |
| Mgi Jnum | J:221255 | Mgi Id | MGI:5638801 |
| Doi | 10.1038/ncomms5410 | Citation | Lee MR, et al. (2014) The adipokine Retnla modulates cholesterol homeostasis in hyperlipidemic mice. Nat Commun 5:4410 |
| abstractText | 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-alpha-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. |
