Fig. 4: YAP/TAZ promote adipocyte survival by suppression of Bim expression.

a Quantitative RT-PCR showing mRNA expression of Yap, Taz, and their target genes including pro- and anti-apoptotic factors in white adipocytes isolated from WT and Ad-Yap/Taz-KO mice fed HFD for 4 weeks (n = 3 mice per group). b RNA-seq data showing expression of Bim (Bcl2l11) in white adipocytes isolated from WT and Ad-Yap/Taz-KO mice fed HFD or standard diet for 4 weeks (n = 2 mice per group). c Expression of Bim in isolated adipocytes from the vWAT of lean (BMI < 25) and obese humans (BMI > 30) (n = 9 in both groups). d Chromatin immunoprecipitation (ChIP) PCR of the TEAD-binding site in the Bim promoter region in lysates of vWAT prepared from WT mice fed standard diet (SD) or HFD for 4 weeks using an anti-YAP antibody (#4912, Cell Signaling Technology) (n = 4 mice per group). e, f Western blot analysis showing BIM protein level in white adipocyte isolated from WT and Ad-Yap/Taz-KO mice (KO) fed HFD for 4 weeks (e) and in adipocytes differentiated from the SVF of WT and Ad-Yap/Taz-KO mice (KO) (f). g Apoptotic cell death detected by TUNEL staining of adipocytes differentiated from SVF of WT and Ad-Yap/Taz-KO mice (n = 5 mice per group). h Quantitative RT-PCR showing mRNA expression of YAP/TAZ target genes in differentiated 3T3-L1 adipocytes treated with control siRNA or siRNA directed against Yap and Taz (n = 3). i, j Differentiated 3T3-L1 adipocytes were treated with control siRNA or siRNA directed against Yap, Taz, and Bim, and western blot analysis was performed to analyze protein levels of BIM, YAP, TAZ, and GAPDH (i). In parallel, cells were analyzed by TUNEL staining to determine cell apoptosis (j) (n = 4). k Bim expression in adipocytes isolated from vWAT 4 weeks after injection of adeno-associated virus transducing control shRNA (AAV-Con) or shRNA directed against Bim (AAV-shBim) fed HFD (n = 3 mice per group). l, m Quantification of crown-like structures (CLS) (l) and of TUNEL-positive cells (m) in sections of vWAT from WT and Ad-Yap/Taz-KO mice 4 weeks after injection of adeno-associated virus transducing control shRNA (AAV-Con) or shRNA directed against Bim (AAV-shBim) and fed HFD (n = 3 mice per group, at least 10 sections were analyzed per animal). Data are presented as the mean ± SEM; *p ≤ 0.05 and **p ≤ 0.01 (unpaired Student’s t-test in a, c, g, h and one-way ANOVA in b, d, j–m). Source data are provided as a Source Data file.