Adipose Subtype-Selective Recruitment of TLE3 or Prdm16 by PPAR¦Ã Specifies Lipid Storage versus Thermogenic Gene Programs

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• 作者：Claudio J. Villanueva¹ ; ² ; ⁹ ; Laurent Vergnes³ ; Jiexin Wang¹ ; ² ; Brian G. Drew⁴ ; ⁵ ; Cynthia Hong¹ ; ² ; Yiping Tu⁴ ; ⁶ ; Yan Hu⁴ ; ⁶ ; Xu Peng⁷ ; Feng Xu⁷ ; Enrique Saez⁸ ; Kevin Wroblewski¹ ; ² ; Andrea L. Hevener⁴ ; ⁵ ; Karen Reue³ ; Loren G. Fong⁴ ; ⁶ ; Stephen G. Young³ ; ⁴ ; ⁶ ; Peter Tontonoz¹ ; ² ; ^{ptontonoz@mednet.ucla.edu}
• 刊名：Cell Metabolism
• 出版年：2013
• 出版时间：5 March, 2013
• 年：2013
• 卷：17
• 期：3
• 页码：423-435
• 全文大小：2413 K

文摘

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Summary

Transcriptional effectors of white adipocyte-selective?gene expression have not been described. Here we show that TLE3 is a white-selective cofactor that acts reciprocally with the brown-selective cofactor Prdm16 to specify lipid storage and thermogenic gene programs. Occupancy of TLE3 and Prdm16 on certain promoters is mutually exclusive, due to the ability of TLE3 to disrupt the physical interaction between Prdm16 and PPAR¦Ã. When expressed at elevated levels in brown fat, TLE3 counters Prdm16, suppressing brown-selective genes and inducing white-selective genes, resulting in impaired fatty acid oxidation and thermogenesis. Conversely, mice lacking TLE3 in adipose tissue show enhanced thermogenesis in inguinal white adipose depots and are protected from age-dependent deterioration of brown adipose tissue function. Our results suggest that the establishment of distinct adipocyte phenotypes with different capacities for thermogenesis and lipid storage is accomplished in part through the cell-type-selective recruitment of TLE3 or Prdm16 to key adipocyte target genes.