Salicylate improves macrophage cholesterol homeostasis via activation of Ampk
Morgan D Fullerton, Rebecca J Ford, Chelsea P McGregor, Nicholas D LeBlond, Shayne A Snider, Stephanie A Stypa, Emily A Day, Sarka Lhotak, Jonathan D Schertzer, Richard C Austin, Bruce E Kemp, Gregory R Steinberg
JOURNAL OF LIPID RESEARCH | ELSEVIER | Published : 2015
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 salicyla..View full abstract
These studies were supported by grants from the Heart and Stroke Foundation of Canada (HSFC) (G.R.S. and R.C.A.), the Canadian Institutes of Health Research (CIHR) (R.C.A. and J.D.S.), the Australian National Health and Medical Research Council and the Victorian Government's Operational Infrastructure Support Program (B.E.K.), as well as start-up funds from the Faculty of Medicine at the University of Ottawa (M.D.F.). M.D.F. was supported by a CIHR Banting Postdoctoral Fellowship and a CIHR Fellowship, J.D.S. is a CDA Scholar, R.C.A. is a Heart and Stroke Foundation of Canada Career Investigator, and G.R.S. is a Canada Research Chair in Metabolism and Obesity and the J. Bruce Duncan Chair in Metabolic Diseases.