title: The adipokine Retnla modulates cholesterol homeostasis in hyperlipidemic mice.
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.
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Chae-ji
authors.initials: CJ
authors.lastname: Lim
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: You-Han
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Jong-Gil
authors.initials: JG
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Seong Keun
authors.initials: SK
authors.lastname: Sonn
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Mi-Ni
authors.initials: MN
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: In-Hyuk
authors.initials: IH
authors.lastname: Jung
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Sejin
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Food and Nutrition, Sungshin Women's University, #249-1, 3-ga, Dongsun-dong, Sungbuk-ku, Seoul 136-742, Republic of Korea.
authors.forename: Myoungsook
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Life Science, Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Ki Sook
authors.initials: KS
authors.lastname: Oh
authors.affiliation: Department of Life Science, Research Center for Women's Disease, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Creative Research Initiatives Center for Adipose Tissue Remodeling, Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
authors.affiliation: National Creative Research Initiatives Center for Nuclear Receptor Signals, Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-751, Republic of Korea.
authors.forename: Hueng-Sik
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Woojin
authors.initials: W
authors.lastname: Jeong
authors.affiliation: National Research Laboratory of Lipid Metabolism & Atherosclerosis, KRIBB, Daejeon 305-806, Republic of Korea.
authors.forename: Tae-Sook
authors.initials: TS
authors.lastname: Jeong
authors.affiliation: Biomedical Mouse Resource Center, KRIBB, Chungbuk 363-883, Republic of Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Yoon
authors.affiliation: Biomedical Mouse Resource Center, KRIBB, Chungbuk 363-883, Republic of Korea.
authors.forename: Hyoung Chin
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Life Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; C413576:Retnla protein, mouse; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase