SIRT3 (Sirtuin-3) Prevents Ang II (Angiotensin II)–Induced Macrophage Metabolic Switch Improving Perivascular Adipose Tissue Function

Objective: Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the microenvironment of hypertensive mice. However, role initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), NAD-dependent deacetylase, is sensitive to status mediates adaptation responses. In this study, we investigated SIRT3-mediated shift regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation. Approach Results: Here, report that Ang II (angiotensin II) accelerates fibrosis, accompanied by activation IL (interleukin)-1? secretion myeloid knockout (SIRT3 ?/ ? ) This effect associated with mitochondrial dysfunction. vitro studies indicate deletion bone marrow–derived induces IL-1? production shifting phenotype from oxidative phosphorylation glycolysis. Mechanistically, deacetylates activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, loss leads PDH activity decrease lactate accumulation. Knocking down LDHA (lactate A) or using carnosine, buffer against lactic acid, attenuates secretion. Furthermore, blockade into brown adipocytes restores thermogenic markers oxygen consumption. Moreover, (NLRP3 ?/? mice exhibited reduced while rescuing function alleviating fibrosis. Conclusions: represents potential therapeutic target attenuate NLRP3-related inflammation. Pharmacological targeting glycolytic metabolism may an effective approach.