{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang X"],"funding":["BLRD VA","NIDDK NIH HHS","NHLBI NIH HHS","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","NCI NIH HHS","American Diabetes Association","U.S. Department of Veterans Affairs","NIGMS NIH HHS"],"pagination":["110-125"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7053091"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2(1)"],"pubmed_abstract":["High protein diets are commonly utilized for weight loss, yet have been reported to raise cardiovascular risk. The mechanisms underlying this risk are unknown. Here, we show that dietary protein drives atherosclerosis and lesion complexity. Protein ingestion acutely elevates amino acid levels in blood and atherosclerotic plaques, stimulating macrophage mTOR signaling. This is causal in plaque progression as the effects of dietary protein are abrogated in macrophage-specific Raptor-null mice. Mechanistically, we find amino acids exacerbate macrophage apoptosis induced by atherogenic lipids, a process that involves mTORC1-dependent inhibition of mitophagy, accumulation of dysfunctional mitochondria, and mitochondrial apoptosis. Using macrophage-specific mTORC1- and autophagy-deficient mice we confirm this amino acid-mTORC1-autophagy signaling axis in vivo. Our data provide the first insights into the deleterious impact of excessive protein ingestion on macrophages and atherosclerotic progression. Incorporation of these concepts in clinical studies will be important to define the vascular effects of protein-based weight loss regimens."],"journal":["Nature metabolism"],"pubmed_title":["High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy."],"pmcid":["PMC7053091"],"funding_grant_id":["T32 HL134635","R01 HL107594","R01 DK115867","R01 HL116626","P30 DK020579","I01 BX003415","R01 CA218578","P30 DK056341","R01 HL125838","I01 BX004235","R01 HL143431","P41 GM103422","#1-18-IBS-029","R01 DK118333"],"pubmed_authors":["Mittendorfer B","Evans TD","Lodhi IJ","Razani B","Sergin I","Holloway KB","Song E","Diwan A","Weihl CC","Stitziel NO","Schilling JD","Crowley JR","Zhang X","Jeong SJ","Rodriguez-Velez A","Chen S","Kapoor D","Epelman S","Fan D"],"additional_accession":[]},"is_claimable":false,"name":"High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy.","description":"High protein diets are commonly utilized for weight loss, yet have been reported to raise cardiovascular risk. The mechanisms underlying this risk are unknown. Here, we show that dietary protein drives atherosclerosis and lesion complexity. Protein ingestion acutely elevates amino acid levels in blood and atherosclerotic plaques, stimulating macrophage mTOR signaling. This is causal in plaque progression as the effects of dietary protein are abrogated in macrophage-specific Raptor-null mice. Mechanistically, we find amino acids exacerbate macrophage apoptosis induced by atherogenic lipids, a process that involves mTORC1-dependent inhibition of mitophagy, accumulation of dysfunctional mitochondria, and mitochondrial apoptosis. Using macrophage-specific mTORC1- and autophagy-deficient mice we confirm this amino acid-mTORC1-autophagy signaling axis in vivo. Our data provide the first insights into the deleterious impact of excessive protein ingestion on macrophages and atherosclerotic progression. Incorporation of these concepts in clinical studies will be important to define the vascular effects of protein-based weight loss regimens.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2024-11-06T04:36:05.667Z","creation":"2020-07-04T07:19:12Z"},"accession":"S-EPMC7053091","cross_references":{"pubmed":["32128508"],"doi":["10.1038/s42255-019-0162-4"]}}