title: NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol transport in ApoE KO mice with high-fat-induced insulin resistance.
abstract: NAMPT has been suggested association with atherosclerosis and insulin resistance. However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the objective of this study was to use a NAMPT loss-of-function approach to investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice. We demonstrated that a specific NAMPT knockdown increased plasma HDL-C levels, reduced the plaque area of the total aorta en face and the cross-sectional aortic sinus, decreased macrophage number and apoptosis, and promoted RCT in HFD-fed ApoE KO mice. These changes were accompanied by increased PPARα, LXRα, ABCA1 and ABCG1 expressions in the liver. NAMPT knockdown also facilitated cholesterol efflux in RAW264.7 cells. We further investigated the effect of NAMPT knockdown on the PPARα-LXRα pathway of cholesterol metabolism with MK886 (a selective inhibitor of PPARα) in RAW264.7 macrophages. MK886 abolished the ability of NAMPT knockdown to decrease intracellular cholesterol levels to enhance the rate of (3)H-cholesterol efflux and to increase ABCA1/G1 and LXRα expressions in RAW264.7 macrophages. Our observations demonstrate that NAMPT knockdown exerted antiatherogenic effects by promoting cholesterol efflux and macrophage RCT through the PPARα- LXRα- ABCA1/G1pathway in vitro and in vivo.
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Shengbing
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Tian
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Junying
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Endocrinology, the Affiliated Hospital, Zunyi Medical College, 563003 Guizhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: The Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Guenther
authors.initials: G
authors.lastname: Boden
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi, MS 39216-4505, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood*; D016207:Cytokines / Q000172:deficiency*; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D054409:Nicotinamide Phosphoribosyltransferase / Q000172:deficiency*; D000067996:RAW 264.7 Cells
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D016207:Cytokines; D004041:Dietary Fats; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse