Salicylate improves macrophage cholesterol homeostasis via activation of Ampk.

Journal of Lipid Research
Morgan D FullertonGregory R Steinberg

Abstract

Atherosclerosis stems from imbalances in lipid metabolism and leads to maladaptive inflammatory responses. The AMP-activated protein kinase (Ampk) is a highly conserved serine/threonine kinase that regulates many aspects of lipid and energy metabolism, although its specific role in controlling macrophage cholesterol homeostasis remains unclear. We sought to address this question by testing the effects of direct Ampk activators in primary bone marrow-derived macrophages from Ampk β1-deficient (β1(-/-)) mice. Macrophages from Ampk β1(-/-) mice had enhanced lipogenic capacity and diminished cholesterol efflux, although cholesterol uptake was unaffected. Direct activation of Ampk β1 via salicylate (the unacetylated form of aspirin) or A-769662 (a small molecule activator), decreased the synthesis of FAs and sterols in WT but not Ampk β1(-/-) macrophages. In lipid-laden macrophages, Ampk activation decreased cholesterol content (foam cell formation) and increased cholesterol efflux to HDL and apoA-I, effects that occurred in an Ampk β1-dependent manner. Increased cholesterol efflux was also associated with increased gene expression of the ATP binding cassette transporters, Abcg1 and Abca1. Moreover, in vivo reverse cholesterol trans...Continue Reading

References

Dec 1, 1989·British Journal of Clinical Pharmacology·R O DayP N Sambrook
Mar 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·G A HiggsJ R Vane
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·J D SmithM Miyata
May 23, 1998·Annual Review of Pharmacology and Toxicology·J R VaneR M Botting
Oct 17, 2001·The Journal of Clinical Investigation·G ZhouD E Moller
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 24, 2002·Circulation Research·Göran K HanssonZhong-Qun Yan
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Feb 8, 2005·The Journal of Biological Chemistry·Tristan J IseliDavid Stapleton
Sep 6, 2005·Journal of Atherosclerosis and Thrombosis·Qaisar Khan, Jawahar L Mehta
Dec 2, 2005·Nature·Frederick R Maxfield, Ira Tabas
Dec 17, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Ingrid C GelissenWendy Jessup
May 27, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Kathryn J Moore, Mason W Freeman
Jun 2, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Ming-Dong WangYves L Marcel
Jul 28, 2007·The Journal of Clinical Investigation·Xun WangDaniel J Rader
Sep 15, 2007·The Journal of Biological Chemistry·Olga GöranssonKei Sakamoto
Nov 28, 2007·Annual Review of Pathology·Göran K HanssonCecilia Söderberg-Nauclér
Dec 10, 2008·Journal of Lipid Research·Daniel J RaderGeorge H Rothblat
Jul 9, 2009·Physiological Reviews·Gregory R Steinberg, Bruce E Kemp
Sep 3, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Julian M W QuinnB J W van Denderen
Sep 25, 2009·The Journal of Biological Chemistry·Xinbing HanWilliam A Boisvert
Nov 3, 2009·Vascular Pharmacology·Shobha GhoshJingmei Song
Nov 7, 2009·The Journal of Biological Chemistry·Nicolas DzamkoBruce E Kemp
Dec 5, 2009·American Heart Journal·Gregory G SchwartzUNKNOWN dal-OUTCOMES Committees and Investigators
Jan 14, 2011·The New England Journal of Medicine·Amit V KheraDaniel J Rader
Nov 15, 2011·The Journal of Clinical Investigation·Sandra GalicGregory R Steinberg
Nov 17, 2011·The New England Journal of Medicine·William E BodenWilliam Weintraub
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·D Grahame HardieSimon A Hawley
Apr 21, 2012·Science·Simon A HawleyD Grahame Hardie
Sep 11, 2012·Nature Medicine·Daniel J Rader, Alan R Tall
Sep 20, 2012·Current Cardiology Reports·Daniel B LarachDaniel J Rader
Feb 23, 2013·Cellular and Molecular Life Sciences : CMLS·Bart LegeinEsther Lutgens

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Citations

Jul 18, 2016·The Journal of Nutritional Biochemistry·Merla J Hubler, Arion J Kennedy
Apr 2, 2016·Experimental & Molecular Medicine·Joungmok KimJoohun Ha
Jun 28, 2016·The International Journal of Biochemistry & Cell Biology·Marina KemmererDmitry Namgaladze
Mar 23, 2017·British Journal of Pharmacology·Fatima IqbalDemidmaa Tuvdendorj
May 26, 2017·Molecular Oncology·Vanessa P HoudeGregory R Steinberg
Jun 26, 2017·Trends in Endocrinology and Metabolism : TEM·Emily A DayGregory R Steinberg
Dec 6, 2017·Cell Biology International·Rong KeDeqiang Huang
Apr 7, 2018·BMC Complementary and Alternative Medicine·Ennian LengWenna Li
Jun 9, 2018·The Journal of Biological Chemistry·Shayne A SniderMorgan D Fullerton
Sep 20, 2017·Nature Communications·Toby A DiteJonathan S Oakhill
Mar 15, 2019·Nature Reviews. Drug Discovery·Gregory R Steinberg, David Carling
Sep 27, 2019·Pharmacological Reviews·Dongdong WangAtanas G Atanasov
Dec 1, 2020·Inflammatory Bowel Diseases·Suhrid BanskotaWaliul I Khan
Sep 27, 2020·Journal of Lipid Research·Nicholas D LeBlondMorgan D Fullerton
Jan 16, 2021·Experimental Physiology·Xiujin ShiYang Lin
Dec 6, 2019·Journal of Ethnopharmacology·Dongdong WangVerena M Dirsch
Dec 3, 2020·International Journal of Molecular Sciences·Nicholas D LeBlondMorgan D Fullerton
Feb 4, 2021·Journal of Lipid Research·Nicholas D LeBlondMorgan D Fullerton
May 28, 2021·Drug Design, Development and Therapy·Yingnan ZhaoJinhan He
Aug 24, 2021·Molecular Metabolism·Emily A DayGregory R Steinberg

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Methods Mentioned

BETA
scraping
flow cytometry
protein knockout
transfection

Clinical Trials Mentioned

NCT00624923

Software Mentioned

GraphPad Prism
FlowJo

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