TY - JOUR T1 - Foam cell induction activates AMPK but uncouples its regulation of autophagy and lysosomal homeostasis JF - bioRxiv DO - 10.1101/2020.08.13.244640 SP - 2020.08.13.244640 AU - Nicholas D. LeBlond AU - Julia R. C. Nunes AU - Tyler K.T. Smith AU - Sabrina Robichaud AU - Suresh Gadde AU - Marceline Cote AU - Bruce Kemp AU - Mireille Ouimet AU - Morgan D. Fullerton Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/08/13/2020.08.13.244640.abstract N2 - 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 of key components in the lysosomal expression and regulation network. Moreover, AMPK activation resulted in targeted up-regulation of members of this network via transcription factor EB. However, in lipid-induced macrophage foam cells, neither basal AMPK signaling nor its activation affected lysosomal-associated programs. These results suggest that while the sum of AMPK signaling in cultured macrophages may be anti-atherogenic, atherosclerotic input dampens the regulatory capacity of AMPK signaling.Competing Interest StatementThe authors have declared no competing interest. ER -