Metformin and AMP Kinase Activation Increase Expression of the Sterol Transporters ABCG5/8 (ATP-Binding Cassette Transporter G5/G8) With Potential Antiatherogenic Consequences

Arteriosclerosis, Thrombosis, and Vascular Biology
Matthew M MoluskyAlan R Tall

Abstract

The mechanisms underlying the cardiovascular benefit of the anti-diabetic drug metformin are poorly understood. Recent studies have suggested metformin may upregulate macrophage reverse cholesterol transport. The final steps of reverse cholesterol transport are mediated by the sterol transporters, ABCG5 (ATP-binding cassette transporter G5) and ABCG8 (ATP-binding cassette transporter G8), which facilitate hepato-biliary transport of cholesterol. This study was undertaken to assess the possibility that metformin induces Abcg5 and Abcg8 expression in liver and to elucidate the underlying mechanisms. Metformin-treated mouse or human primary hepatocytes showed increased expression of Abcg5/8 and the bile salt export pump, Bsep. Administration of metformin to Western-type diet-fed mice showed significant upregulation of Abcg5/8 and Bsep. This resulted in increased initial clearance of 3H-cholesteryl ester HDL (high-density lipoprotein) from plasma. However, fecal 3H-cholesterol output was only marginally increased, possibly reflecting increased hepatic Ldlr (low-density lipoprotein receptor) expression, which would increase nonradiolabeled cholesterol uptake. Abcg5/8 undergo strong circadian variation. Available chromatin immunoprec...Continue Reading

References

Nov 1, 1975·The American Journal of Physiology·K J Ho, J L Drummond
Aug 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·H M Sobell
Jan 1, 1986·Methods in Enzymology·J H Tollefson, J J Albers
Apr 7, 1973·Lancet·T C Northfield, A F Hofmann
Jul 1, 1972·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·C J Bailey, A J Matty
Feb 15, 1973·The New England Journal of Medicine·A L MetzgerS M Grundy
Dec 1, 1969·Archives of Biochemistry and Biophysics·J A WatsonJ M Lowenstein
Apr 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N HeninG Van den Berghe
Dec 22, 1999·Current Opinion in Biotechnology·J J Repa, D J Mangelsdorf
Mar 20, 2002·The Journal of Biological Chemistry·Joyce J RepaDavid J Mangelsdorf
May 23, 2002·Cell·Satchidananda PandaJohn B Hogenesch
Nov 22, 2002·Proceedings of the National Academy of Sciences of the United States of America·Liqing YuHelen H Hobbs
Oct 29, 2004·Journal of Cell Science·D Grahame Hardie
Jun 16, 2005·American Journal of Physiology. Endocrinology and Metabolism·Murwarid M AssifiNeil B Ruderman
Jul 12, 2005·Oncogene·Daniel E BauerCraig B Thompson
Oct 18, 2005·Cancer Cell·Georgia HatzivassiliouCraig B Thompson
Mar 27, 2007·Bioorganic & Medicinal Chemistry Letters·James J LiThomas Harrity
May 15, 2007·Science·David Gatfield, Ueli Schibler
Jul 1, 2008·Nature Medicine·Sudha B BiddingerC Ronald Kahn
Nov 15, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·William R LagorDaniel J Rader
Dec 9, 2008·Nature Genetics·Sekar KathiresanL Adrienne Cupples
Mar 17, 2009·Journal of Lipid Research·Zhengping MaDong Cheng
Apr 4, 2009·PLoS Genetics·Michael E HughesJohn B Hogenesch
May 23, 2009·Science·Kathryn E WellenCraig B Thompson

❮ Previous
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Citations

Dec 1, 2018·PLoS Biology·Anand R SaranLuciano DiTacchio
Dec 24, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Dec 14, 2019·Chronobiology International·Norifumi TateishiShigenobu Shibata
Dec 27, 2018·Current Opinion in Lipidology·Amy C BurkeMurray W Huff
Jun 27, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Henry H RuizAnn Marie Schmidt
Aug 11, 2020·Nutrition & Metabolism·Zixiang YeTao Wu
Jan 8, 2020·Pharmaceutical Research·Brandy GarzelHongbing Wang
Dec 21, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Amrita Devi KhwairakpamAjaikumar B Kunnumakkara
Sep 10, 2019·Progress in Lipid Research·Xiaojun FengAi-Zong Shen
Jan 28, 2021·Cardiovascular Drugs and Therapy·Andrey V SusekovGerald F Watts
Dec 7, 2020·Cellular and Molecular Gastroenterology and Hepatology·Dayan SunLi Jin
Apr 4, 2021·International Journal of Molecular Sciences·Kori WilliamsGregory A Graf
May 28, 2021·Drug Design, Development and Therapy·Yingnan ZhaoJinhan He
Jun 25, 2021·Frontiers in Immunology·Xiaojun FengJianping Weng

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Methods Mentioned

BETA
PCR
immunoprecipitation
pull down
Protein Assay
immunoprecipitation assay
ChIP
acetylation
transgenic

Software Mentioned

GraphPad
Prism

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