Journal article

Foam Cell Induction Activates AMPK But Uncouples Its Regulation of Autophagy and Lysosomal Homeostasis

Nicholas D LeBlond, Julia RC Nunes, Tyler KT Smith, Conor D'Dwyer, Sabrina Robichaud, Suresh Gadde, Marceline Cote, Bruce E Kemp, Mireille Ouimet, Morgan D Fullerton

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | MDPI | Published : 2020

Abstract

The dysregulation of macrophage lipid metabolism drives atherosclerosis. AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics and plays essential roles regulating macrophage lipid dynamics. Here, we investigated the consequences of atherogenic lipoprotein-induced foam cell formation on downstream immunometabolic signaling in primary mouse macrophages. A variety of atherogenic low-density lipoproteins (acetylated, oxidized, and aggregated forms) activated AMPK signaling in a manner that was in part due to CD36 and calcium-related signaling. In quiescent macrophages, basal AMPK signaling was crucial for maintaining markers of lysosomal homeostasis as well as levels ..

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University of Melbourne Researchers

Grants

Awarded by Canadian Institutes of Health Research (CIHR)


Awarded by CIHR New Investigator award


Awarded by New Frontiers Research Fund Exploration grant


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Funding Acknowledgements

This research was funded by project grants from the Canadian Institutes of Health Research (CIHR) (PJT148634 to M.D.F and PJT391187 to M.O) and a CIHR New Investigator award (MSH141981 to M.D.F.), an Early Research Leadership Initiative from the Heart and Stroke Foundation of Canada and its partners (M.D.F), a Heart and Stroke Foundation of Canada Grant-in-Aid (to M.O.), an Ontario Ministry of Research, Innovation and Science Early Researcher Award (M.D.F), and a New Frontiers Research Fund Exploration grant (NFRFE-2018-01842 to M.C., S.G., and M.D.F.). M.C. and M.O. are Canada Research Chairs in Molecular Virology and Antiviral Therapeutics, and Cardiovascular Biology, respectively. BEK was supported by the National Health and Medical Research Council of Australia (NHMRC) project grant (1085460) and Fellowship (1078752). Ontario Graduate Scholarships supported N.D.L, T.K.T.S., and J.R.C.N. and a Canada Graduate Scholarship Master's supported S.R.