Fig 2: Synopsis of this study. EOD, early-onset type 2 diabetes; MAF, minor allele frequency; PPARG-DM, PPARγ variant-induced diabetes; ACMG, American College of Medical Genetics.

Fig 3: REDD1 elicits adipocyte differentiation and macrophage inflammation through NF-κB activation.a–c Representative oil red-O (ORO)-stained images of WT and Redd1−/− SVF cells (a), shControl (shC)- or sh-Redd1-transfected 3T3-L1 cells (b), and WT (Redd1fl/fl, Rfl/fl) and Redd1ΔAdipoq (RΔAdipoq) SVF cells (c) when cultured in differentiation medium (MDI) and quantification of relative ORO intensity (n = 4). d–f, Expression levels of adipogenic genes (d), REDD1 (e), and lipogenic genes (f) in Rfl/fl and RΔAdipoq SVF cells cultured in MDI medium and quantification of relative ORO intensity (n = 4). g Assessment of NF-κB–Luc activity in 3T3-L1 cells transfected either with siRNA for control, Ikka, Ikkb, or NF-κB p65 (p65) or with pcDNA3.1/His-Ikba (n = 5). h, i Representative images and realative quantification of ORO-stained images (h) and expression levels of Pparg and Cebpa (i) in 3T3-L1 cells infected with control adenovirus (Ad-C) or adenoviral Redd1 (Ad-R) after transfection with vector alone or pcDNA3.1/His-Ikba (n = 4). j NF-κB–Luc activity in mouse peritoneal macrophages infected with Ad-C or Ad-Redd1 (n = 4). k Cytokine production in mouse peritoneal macrophages infected with Ad-C or Ad-Redd1 (n = 5). Bar graphs represent mean ± s.e.m. Statistical significance was calculated using one-way ANOVA (g, h) and two-way ANOVA (a, i) followed by the Holm–Sidak post hoc test and an unpaired two-tailed t-test (b–f, j, k). Source data are provided as a Source Data file.

Fig 4: PPARG radiosensitize A549 cells. A549 cells were transfected with PPARG and irradiated 24 h post-transfection and processed 48 h after transfection. The groups included CONTROL, RAD CONTROL (5 Gy), PPARG (TT), and RAD+PPARG (TT). The cells were processed for various assays. (A) Morphological analysis was done 24 h post-radiation (48 h post PPARG transfection). (B) Cell count was determined using hemocytometer 24 h post-radiation. The error bar represents standard deviation in which ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. The experiment was done in triplicate (n = 3) and repeated three times (C) cell viability was assessed by MTT assay 24 h post-radiation. The error bar represents standard deviation in which ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. The experiment was done in triplicate (n = 3) and repeated three times. (D) Cell viability was assessed by SRB (Sulforhodamine) assay 24 h post-radiation. The error bar represents standard deviation in which ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. The experiment was done in triplicate (n = 3).

Fig 5: Suppression of hepatocarcinogenesis following HSF1 inactivation is accompanied by downregulation of activated AKT and its downstream effectors in the mouse liver(A, B) Representative Western blot analysis of livers from control mice (injected with empty vector), AKT mice (injected with myr-AKT1) and AKT/HSF1dn mice (co-injected with myr-AKT1 and HSF1dn). Inactivation of HSF1 in AKT/HSF1dn mice resulted in downregulation of phosphorylated/activated AKT. Levels of some AKT upstream (PIK3CA) and downstream effectors (p-RPS6, p-NDRG1, FASN, ACLY, ACAC, SCD1, PPARG, ALDOA, LDHA/C, PKM2) were downregulated in AKT/HSF1dn mice when compared with AKT mice. As expected, livers from AKT/HSF1dn mice were the only ones to express the transfected HSF1dn construct (V5-tagged). Of note, the levels of some of the proteins tested were even lower in AKT/HSF1dn mice than in control mice. Ten livers from each group of mice were used for the analysis, and representative images are shown. β-Actin was used as a loading control. (C–F) Fatty acid biosynthesis, cholesterol and triglyceride content, and lactate dehydrogenase activity were strongly induced in the livers of AKT mice, and equally lower in control and AKT/HSF1dn livers. Tukey–Kramer test: P < 0.0001 a, vs control (mice injected with empty vector); b, vs AKT mice. Abbreviations: FA, fatty acid; CE, cholesterol; TG, triglycerides; LDH, lactate dehydrogenase.