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Activation of BAT via 48\u2009h cold (16\u00b0C) in mice following transverse aortic constriction (TAC) reduced cardiac gene expression for LCFA uptake and oxidation in male mice and accelerated the onset of cardiac metabolic remodeling, with an early isoform shift of carnitine palmitoyltransferase 1 (CPT1) toward increased CPT1a, reduced entry of long chain fatty acid (LCFA) into oxidative metabolism (0.59\u2009\u00b1\u20090.02 vs. 0.72\u2009\u00b1\u20090.02 in RT TAC hearts,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05) and increased carbohydrate oxidation with altered glucose transporter content. BAT activation with TAC reduced early hypertrophic expression of \u03b2\u2010MHC by 61% versus RT\u2010TAC and reduced pro\u2010fibrotic TGF\u2010\u03b21 and COL3\u03b11 expression. While cardiac natriuretic peptide expression was yet to increase at only 3\u2009days TAC,\n                    <jats:italic>Nppa<\/jats:italic>\n                    and\n                    <jats:italic>Nppb<\/jats:italic>\n                    expression were elevated in Cold TAC versus RT TAC hearts 2.7\u2010 and 2.4\u2010fold, respectively. Eliminating BAT thermogenic activation with UCP1 KO mice eliminated differences between Cold TAC and RT TAC hearts, confirming effects of BAT activation rather than autonomous cardiac responses to cold. Female responses to BAT activation were blunted, with limited UCP1 changes with cold, partly due to already activated BAT in females at RT compared to thermoneutrality. These data reveal a previously unknown physiological mechanism of UCP1\u2010dependent BAT activation in attenuating early cardiac hypertrophic and profibrotic signaling and accelerating remodeled metabolic activity in the heart at the onset of cardiac stress.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400922r","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T12:20:43Z","timestamp":1716985243000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>UCP1<\/scp>\n                    \u2010dependent brown adipose activation accelerates cardiac metabolic remodeling and reduces initial hypertrophic and fibrotic responses to pathological stress"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-1692","authenticated-orcid":false,"given":"Azariyas A.","family":"Challa","sequence":"first","affiliation":[{"name":"Department of Internal 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