Fig. 5. TFE3 suppresses SREBP-1c proteolytic processing and activation.
(A to D) Control, LiFKO, and DKO mice were fed an FPC diet regimen (TD190142 with sugar water) for 9 days and euthanized at 10 p.m. ad lib (n = 7 to 9). One-way ANOVA with Tukey’s multiple comparisons test was used. (A) Body weights. (B) mRNA expression of DNL genes. (C) Liver protein expression of SREBP-1, INSIG2, and beta actin. AAV-1c, positive control from liver injected with AAV8 expressing constitutively nuclear SREBP-1c; P, precursor form of SREBP-1; N, nuclear (processed) form of SREBP-1. (D) Genome browser tracks of the Insig2 promoter. Depicted are TFE3 ChIP-seq tracks (described in Fig. 3F) from one representative sample per genotype. (E) Schematic of FLCN:TFE3 regulation of SREBP-1c proteolytic processing. (F to J) Flcnlox/lox mice (n = 5 or 6) were injected with either “control virus” (AAV8-GFP or AAV8-Cre; to generate control or LiFKO mice) or AAV8-ApoE/AAT-HA-nSREBP-1c (“1c”) and then maintained for 9 days on an FPC diet (TD190142 with sugar water). Student’s two-tailed t test was used for analysis. (F) Experimental outline. (G) Body weights. (H) Liver protein expression of exogenous HA-tagged nuclear SREBP-1c (HA), total SREBP-1, INSIG2, and 14-3-3. (I) Hepatic triglyceride quantification. (J) Liver mRNA expression of indicated DNL genes. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data are depicted as mean ± SEM.