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. Author manuscript; available in PMC: 2012 Jul 6.
Published in final edited form as: Cell Metab. 2011 Jul 6;14(1):67–79. doi: 10.1016/j.cmet.2011.04.013

Figure 5. Smad3 regulates the PGC-1α promoter and PRDM16 target genes.

Figure 5

a, Representative heat-map of microarray analyses of WAT from RD or HFD fed WT and KO mice and from diet-induced obese (DIO) mice treated with control IgG or anti-TGF-β1 (α-TGF-β1) antibody. b, Pie-chart classification of “103 signature genes” (represented in the three boxed areas of the heat map) in WAT from RD or HFD-fed KO mice and from DIO mice treated with α-TGF-β antibody, compared to RD or HFD fed WT mice and from DIO mice treated with control IgG, respectively. c, ChIP assays show binding of Smad3 (arrowhead) to the PGC-1α promoter in 3T3-L1 cells. Input and IgG antibody control is shown. d, TGF-β suppresses the PGC-1α-luciferase reporter in 3T3-L1 cells, but not in 3T3-L1 cells expressing shSmad3 lentivirus. e, Smad3 regulates PRDM16 target genes. Control 3T3-L1 cells were infected with lentiviruses expressing GFP (3T3-L1GFP), shPRDM16 (3t3-Li+shPRDM16), shSmad3 (shSmad3+GFP) or shSmad3 and ShPRDM16 together (shSmad3+shPRDM16) followed by real time RT-PCR. Fold change in expression relative to 18S is shown. f, Proposed model for WAT to BAT phenotypic conversion upon loss of Smad3 signaling. Loss of Smad3 leads to enhanced expression of BAT/mitochondrial/muscle-specific transcripts along with reduced expression of WAT-specific genes. The appearance of UCP1+ brown adipocytes in the WAT milieu is promoted by PRDM16. *p < 0.05; **, p< 0.005; ***, p<0.001.