Adiponectin Upregulates ABCA1 Expression Through Liver X Receptor Alpha Signaling Pathway in RAW 264.7 Macrophages

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2015 Mar 11

PMID 25755733

Citations 8

Authors

Bin Liang

Xin Wang

Xiaohong Guo

Zhiming Yang

Rui Bai

Ming Liu

Chuanshi Xiao

Yunfei Bian

Affiliations

Soon will be listed here.

Abstract

ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and anti-atherosclerosis. Liver X receptor alpha (LXRα) can stimulate cholesterol efflux through ABCA1. It has been well known that adiponectin has cardiovascular protection. In this study, we attempted to clarify the effect of adiponectin on expression of ABCA1, and explored the role of LXRα in the regulation of ABCA1 in RAW 264.7 macrophages. Our results showed that adiponectin increased ABCA1 expression at both the mRNA and protein levels in a dose-dependent and time-dependent manner. Consequently, adiponectin promoted cholesterol efflux and decreased cholesterol content in RAW 264.7 macrophages. Moreover, adiponectin up-regulated the expression of LXRα in a dose-dependent and time-dependent manner in RAW 264.7 macrophages. LXRα small interfering RNA completely abolished the promotion effects of adiponectin. In summary, adiponectin up-regulates ABCA1 expression via the LXRα pathway in RAW 264.7 macrophages. This novel insight could prove useful for developing new treatment strategies for cardiovascular diseases.

Citing Articles

Effect of Extract on Foam Cell Formation in THP-1 Macrophages.

Moon H, Yun J Prev Nutr Food Sci. 2024; 29(3):288-300.

PMID: 39371520 PMC: 11450289. DOI: 10.3746/pnf.2024.29.3.288.

Role of Adiponectin in Cardiovascular Diseases Related to Glucose and Lipid Metabolism Disorders.

Han W, Yang S, Xiao H, Wang M, Ye J, Cao L Int J Mol Sci. 2022; 23(24).

PMID: 36555264 PMC: 9779180. DOI: 10.3390/ijms232415627.

Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer's disease.

Horgusluoglu E, Neff R, Song W, Wang M, Wang Q, Arnold M Alzheimers Dement. 2021; 18(6):1260-1278.

PMID: 34757660 PMC: 9085975. DOI: 10.1002/alz.12468.

Stadler J, Marsche G Int J Mol Sci. 2020; 21(23).

PMID: 33256096 PMC: 7731239. DOI: 10.3390/ijms21238985.

The roles of FGF21 in atherosclerosis pathogenesis.

Tabari F, Karimian A, Parsian H, Rameshknia V, Mahmoodpour A, Majidinia M Rev Endocr Metab Disord. 2019; 20(1):103-114.

PMID: 30879171 DOI: 10.1007/s11154-019-09488-x.

References

Escola-Gil J, Rotllan N, Julve J, Blanco-Vaca F . In vivo macrophage-specific RCT and antioxidant and antiinflammatory HDL activity measurements: New tools for predicting HDL atheroprotection. Atherosclerosis. 2009; 206(2):321-7. DOI: 10.1016/j.atherosclerosis.2008.12.044. View

Liang B, Wang X, Bian Y, Yang H, Liu M, Bai R . Angiotensin-(1-7) upregulates expression of adenosine triphosphate-binding cassette transporter A1 and adenosine triphosphate-binding cassette transporter G1 through the Mas receptor through the liver X receptor alpha signalling pathway in THP-1.... Clin Exp Pharmacol Physiol. 2014; 41(12):1023-30. DOI: 10.1111/1440-1681.12312. View

Delvecchio C, Bilan P, Nair P, Capone J . LXR-induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1. Am J Physiol Lung Cell Mol Physiol. 2008; 295(5):L949-57. DOI: 10.1152/ajplung.90394.2008. View

Lee S, Kwak H . Role of adiponectin in metabolic and cardiovascular disease. J Exerc Rehabil. 2014; 10(2):54-9. PMC: 4025550. DOI: 10.12965/jer.140100. 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

Choudhury R, Lee J, Greaves D . Mechanisms of disease: macrophage-derived foam cells emerging as therapeutic targets in atherosclerosis. Nat Clin Pract Cardiovasc Med. 2005; 2(6):309-15. DOI: 10.1038/ncpcardio0195. View

Aravindhan K, Webb C, Jaye M, Ghosh A, Willette R, John DiNardo N . Assessing the effects of LXR agonists on cellular cholesterol handling: a stable isotope tracer study. J Lipid Res. 2006; 47(6):1250-60. DOI: 10.1194/jlr.M500512-JLR200. View

Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M . Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002; 106(22):2767-70. DOI: 10.1161/01.cir.0000042707.50032.19. View

Xu X, Li Q, Pang L, Huang G, Huang J, Shi M . Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway. Biochem Biophys Res Commun. 2013; 441(2):321-6. DOI: 10.1016/j.bbrc.2013.10.050. View

10.

Li S, Shin H, Ding E, van Dam R . Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009; 302(2):179-88. DOI: 10.1001/jama.2009.976. View

11.

Lee C, Tai B, Lim G, Chan M, Low A, Tan K . Correlation between high density lipoprotein-cholesterol and remodeling index in patients with coronary artery disease: IDEAS (IVUS diagnostic evaluation of atherosclerosis in Singapore)-HDL study. Int J Cardiovasc Imaging. 2011; 28(1):33-41. DOI: 10.1007/s10554-010-9777-y. View

12.

Ntaios G, Gatselis N, Makaritsis K, Dalekos G . Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis. 2013; 227(2):216-21. DOI: 10.1016/j.atherosclerosis.2012.12.029. View

13.

Pischon T, Girman C, Hotamisligil G, Rifai N, Hu F, Rimm E . Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004; 291(14):1730-7. DOI: 10.1001/jama.291.14.1730. View

14.

Yuan Y, Li P, Ye J . Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis. Protein Cell. 2012; 3(3):173-81. PMC: 4875426. DOI: 10.1007/s13238-012-2025-6. View

15.

Guo J, Bian Y, Bai R, Li H, Fu M, Xiao C . Globular adiponectin attenuates myocardial ischemia/reperfusion injury by upregulating endoplasmic reticulum Ca²⁺-ATPase activity and inhibiting endoplasmic reticulum stress. J Cardiovasc Pharmacol. 2013; 62(2):143-53. DOI: 10.1097/FJC.0b013e31829521af. View

16.

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

17.

Schmitz G, Langmann T . Structure, function and regulation of the ABC1 gene product. Curr Opin Lipidol. 2001; 12(2):129-40. DOI: 10.1097/00041433-200104000-00006. View

18.

Zhu W, Cheng K, Vanhoutte P, Lam K, Xu A . Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci (Lond). 2008; 114(5):361-74. DOI: 10.1042/CS20070347. View

19.

Pettersson A, Stenson B, Lorente-Cebrian S, Andersson D, Mejhert N, Kratzel J . LXR is a negative regulator of glucose uptake in human adipocytes. Diabetologia. 2013; 56(9):2044-54. DOI: 10.1007/s00125-013-2954-5. View