Effect of Adiponectin on Macrophage Reverse Cholesterol Transport in Adiponectin-/- Mice and Its Mechanism

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2017 Jun 8

PMID 28587337

Citations 3

Authors

Yueru Wang

Xin Wang

Yingying Guo

Yunfei Bian

Rui Bai

Bin Liang

Chuanshi Xiao

Affiliations

Soon will be listed here.

Abstract

The objective of the present study was to investigate the effect of adiponectin (APN) on macrophage reverse cholesterol transport (RCT) in adiponectin-/- knockout mice (APN-/-mice) and its possible anti-atherosclerotic mechanism. A total of 30 male APN-/-mice were randomly divided into the control group and four intervention groups. The intervention groups were treated with intraperitoneal injections of APN, at doses of 50, 150, 200 and 250 µg/(kg/day), respectively, for 4 weeks. The control group received normal saline. After 4 weeks, serum lipid levels were measured, the degree of severity of atherosclerotic lesions was observed by light microscopy, the H-TC (APN-/-mice treated with intraperitoneal injections of H-TC-labeled macrophages) radioactivity in serum, liver, and feces, and the expression of ABCA1 mRNA and protein in liver were determined. Compared with the control group, serum triglycerides, total cholesterol, and low-density lipoproteins levels in the intervention groups were significantly decreased, while high-density lipoprotein was increased. The severity of aortic atherosclerotic lesions in the intervention groups was milder than in the control group, which had obvious aortic atherosclerotic lesions, large lipid deposition on vessel walls, and the formation of atheromatous plaques. In the intervention groups, serum H-TC content was significantly decreased (P<0.05), but the H-TC content in liver and feces was significantly increased (P<0.05). The levels of ABCA1 mRNA in liver of the intervention groups were significantly increased in a dose-dependent manner. In conclusion, APN can promote RCT and intracellular cholesterol efflux by upregulating the expression of ABCA1, to delay the occurrence and development of atherosclerosis.

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References

Zhao Y, Pennings M, Hildebrand R, Ye D, Calpe-Berdiel L, Out R . Enhanced foam cell formation, atherosclerotic lesion development, and inflammation by combined deletion of ABCA1 and SR-BI in Bone marrow-derived cells in LDL receptor knockout mice on western-type diet. Circ Res. 2010; 107(12):e20-31. DOI: 10.1161/CIRCRESAHA.110.226282. View

Rosenson R, Brewer Jr H, Davidson W, Fayad Z, Fuster V, Goldstein J . Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation. 2012; 125(15):1905-19. PMC: 4159082. DOI: 10.1161/CIRCULATIONAHA.111.066589. View

Liang B, Wang X, Guo X, Yang Z, Bai R, Liu M . Adiponectin upregulates ABCA1 expression through liver X receptor alpha signaling pathway in RAW 264.7 macrophages. Int J Clin Exp Pathol. 2015; 8(1):450-7. PMC: 4348878. View

Singh A, Joharapurkar A, Khan M, Mishra J, Singh N, Yadav M . Orally active osteoanabolic agent GTDF binds to adiponectin receptors, with a preference for AdipoR1, induces adiponectin-associated signaling, and improves metabolic health in a rodent model of diabetes. Diabetes. 2014; 63(10):3530-44. DOI: 10.2337/db13-1619. View

Tang C, Tang G, Yi G, Wang Z, Liu L, Wan S . Effect of apolipoprotein A-I on ATP binding cassette transporter A1 degradation and cholesterol efflux in THP-1 macrophage-derived foam cells. Acta Biochim Biophys Sin (Shanghai). 2004; 36(3):218-26. DOI: 10.1093/abbs/36.3.218. View

Glomset J, Norum K . The metabolic role of lecithin: cholesterol acyltransferase: perspectives form pathology. Adv Lipid Res. 1973; 11:1-65. View

Da-Wa C, Zhao F, Qi Y, Chen L, Huo Y . [Role of adiponectin and its receptors in anti-atherosclerotic effects of pioglitazone on ApoE knocked out mice]. Beijing Da Xue Xue Bao Yi Xue Ban. 2009; 41(2):174-8. View

Ohashi R, Mu H, Wang X, Yao Q, Chen C . Reverse cholesterol transport and cholesterol efflux in atherosclerosis. QJM. 2005; 98(12):845-56. DOI: 10.1093/qjmed/hci136. View

Luo R, Li X, Jiang R, Gao X, Lu Z, Hua W . Serum concentrations of resistin and adiponectin and their relationship to insulin resistance in subjects with impaired glucose tolerance. J Int Med Res. 2012; 40(2):621-30. DOI: 10.1177/147323001204000224. View

10.

Donato M, DAnnunzio V, Buchholz B, Miksztowicz V, Carrion C, Valdez L . Role of matrix metalloproteinase-2 in the cardioprotective effect of ischaemic postconditioning. Exp Physiol. 2009; 95(2):274-81. DOI: 10.1113/expphysiol.2009.049874. View

11.

Liu L . Epidemiology of hypertension and cardiovascular disease--China experience. Clin Exp Hypertens A. 1990; 12(5):831-44. View

12.

Doosti M, Najafi M, Zavar Reza J, Nikzamir A . The role of ATP-binding-cassette-transporter-A1 (ABCA1) gene polymorphism on coronary artery disease risk. Transl Res. 2010; 155(4):185-90. DOI: 10.1016/j.trsl.2009.12.002. View

13.

Ciatto C, Bahna F, Zampieri N, VanSteenhouse H, Katsamba P, Ahlsen G . T-cadherin structures reveal a novel adhesive binding mechanism. Nat Struct Mol Biol. 2010; 17(3):339-47. PMC: 2873897. DOI: 10.1038/nsmb.1781. View

14.

Denzel M, Scimia M, Zumstein P, Walsh K, Ruiz-Lozano P, Ranscht B . T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest. 2010; 120(12):4342-52. PMC: 2993592. DOI: 10.1172/JCI43464. View

15.

Khor G . Cardiovascular epidemiology in the Asia-Pacific region. Asia Pac J Clin Nutr. 2001; 10(2):76-80. DOI: 10.1111/j.1440-6047.2001.00230.x. View

16.

Deng Y, Scherer P . Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci. 2011; 1212:E1-E19. PMC: 3075414. DOI: 10.1111/j.1749-6632.2010.05875.x. View

17.

Lewis G, Rader D . New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res. 2005; 96(12):1221-32. DOI: 10.1161/01.RES.0000170946.56981.5c. View

18.

Fitzgerald M, Mujawar Z, Tamehiro N . ABC transporters, atherosclerosis and inflammation. Atherosclerosis. 2010; 211(2):361-70. PMC: 2888932. DOI: 10.1016/j.atherosclerosis.2010.01.011. View

19.

Knoflach M, Kiechl S, Penz D, Zangerle A, Schmidauer C, Rossmann A . Cardiovascular risk factors and atherosclerosis in young women: atherosclerosis risk factors in female youngsters (ARFY study). Stroke. 2009; 40(4):1063-9. DOI: 10.1161/STROKEAHA.108.525675. View

20.

Chung S, Gebre A, Seo J, Shelness G, Parks J . A novel role for ABCA1-generated large pre-beta migrating nascent HDL in the regulation of hepatic VLDL triglyceride secretion. J Lipid Res. 2010; 51(4):729-42. PMC: 2842152. DOI: 10.1194/jlr.M900083. View