{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang SJ"],"funding":["National Natural Science Foundation of China","National Postdoctoral Program for Innovative Talents","National Key Research and Development Program of China"],"pagination":["2003410"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8097358"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(9)"],"pubmed_abstract":["Atherosclerosis is a chronic inflammatory disease that can cause acute cardiovascular events. Activation of the NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome enhances atherogenesis, which links lipid metabolism to sterile inflammation. This study examines the impact of an endogenous metabolite, namely ketone body 3-hydroxybutyrate (3-HB), on a mouse model of atherosclerosis. It is found that daily oral administration of 3-HB can significantly ameliorate atherosclerosis. Mechanistically, 3-HB is found to reduce the M1 macrophage proportion and promote cholesterol efflux by acting on macrophages through its receptor G-protein-coupled receptor 109a (Gpr109a). 3-HB-Gpr109a signaling promotes extracellular calcium (Ca<sup>2+</sup>) influx. The elevation of intracellular Ca<sup>2+</sup> level reduces the release of Ca<sup>2+</sup> from the endothelium reticulum (ER) to mitochondria, thus inhibits ER stress triggered by ER Ca<sup>2+</sup> store depletion. As NLRP3 inflammasome can be activated by ER stress, 3-HB can inhibit the activation of NLRP3 inflammasome, which triggers the increase of M1 macrophage proportion and the inhibition of cholesterol efflux. It is concluded that daily nutritional supplementation of 3-HB attenuates atherosclerosis in mice."],"journal":["Advanced science (Weinheim, Baden-Wurttemberg, Germany)"],"pubmed_title":["Ketone Body 3-Hydroxybutyrate Ameliorates Atherosclerosis via Receptor Gpr109a-Mediated Calcium Influx."],"pmcid":["PMC8097358"],"funding_grant_id":["31870859","21761132013","BX201700130","2018YFA0900200","31771886","31971170"],"pubmed_authors":["Li Y","Wu FQ","Chen J","Chen GQ","Zhang YD","Wang W","Cui ZJ","Zhang SJ","Li ZH"],"additional_accession":[]},"is_claimable":false,"name":"Ketone Body 3-Hydroxybutyrate Ameliorates Atherosclerosis via Receptor Gpr109a-Mediated Calcium Influx.","description":"Atherosclerosis is a chronic inflammatory disease that can cause acute cardiovascular events. Activation of the NOD-like receptor family, pyrin domain containing protein 3 (NLRP3) inflammasome enhances atherogenesis, which links lipid metabolism to sterile inflammation. This study examines the impact of an endogenous metabolite, namely ketone body 3-hydroxybutyrate (3-HB), on a mouse model of atherosclerosis. It is found that daily oral administration of 3-HB can significantly ameliorate atherosclerosis. Mechanistically, 3-HB is found to reduce the M1 macrophage proportion and promote cholesterol efflux by acting on macrophages through its receptor G-protein-coupled receptor 109a (Gpr109a). 3-HB-Gpr109a signaling promotes extracellular calcium (Ca<sup>2+</sup>) influx. The elevation of intracellular Ca<sup>2+</sup> level reduces the release of Ca<sup>2+</sup> from the endothelium reticulum (ER) to mitochondria, thus inhibits ER stress triggered by ER Ca<sup>2+</sup> store depletion. As NLRP3 inflammasome can be activated by ER stress, 3-HB can inhibit the activation of NLRP3 inflammasome, which triggers the increase of M1 macrophage proportion and the inhibition of cholesterol efflux. It is concluded that daily nutritional supplementation of 3-HB attenuates atherosclerosis in mice.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2024-11-12T03:18:19.37Z","creation":"2022-02-10T10:02:37.193Z"},"accession":"S-EPMC8097358","cross_references":{"pubmed":["33977048"],"doi":["10.1002/advs.202003410"]}}