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The molecular mechanism regulating this phenotypic switch remains largely unknown. This study explores the role of tuberous sclerosis complex 1 (TSC1)\u2013mechanistic target of rapamycin (mTOR) signaling in the conversion of brown to white adipose tissue (WAT). A colony of Fabp4-Tsc1\u2212\/\u2212 mice, in which the Tsc1 gene was specifically deleted by the fatty acid binding protein 4 (FABP4)-Cre, was established. Western blotting and immunostaining demonstrated the absence of TSC1 and activation of ribosomal protein S6 kinase 1, the downstream target of mTOR complex 1 (mTORC1) signaling, in the brown adipose tissues (BATs) of Fabp4-Tsc1\u2212\/\u2212 mice. Accumulation of lipid droplets in BAT was significantly increased. Levels of brown adipocyte markers were markedly downregulated, while white adipocyte markers were upregulated. Rapamycin reversed the conversion from BAT to WAT in Fabp4-Tsc1\u2212\/\u2212 mice. Deletion of the Tsc1 gene in cultured brown preadipocytes significantly increased the conversion to white adipocytes. FoxC2 mRNA, the transcriptional factor for brown adipocyte determination, was significantly decreased, while mRNAs for retinoblastoma protein, p107 and RIP140, the transcriptional factors for white adipocyte determination, increased in the BAT of Fabp4-Tsc1\u2212\/\u2212 mice. Our study demonstrates that TSC1-mTORC1 signaling contributes to the brown-to-white adipocyte phenotypic switch.<\/jats:p>","DOI":"10.2337\/db14-0427","type":"journal-article","created":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T07:18:41Z","timestamp":1410506321000},"page":"519-528","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":50,"title":["Tuberous Sclerosis Complex 1\u2013Mechanistic Target of Rapamycin Complex 1 Signaling Determines Brown-to-White Adipocyte Phenotypic Switch"],"prefix":"10.2337","volume":"64","author":[{"given":"Xinxin","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China"},{"name":"Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China"},{"name":"Department of Pathology, Central Hospital of Zibo, Zibo, 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