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. 2020 Oct 30;72(5):1638–1653. doi: 10.1002/hep.31198

FIG. 4.

FIG. 4

Hepatic ChREBP regulates hepatic Mttp and Tm6sf2 expression. (A) Box‐and‐whisker plots presenting hepatic relative levels of VLDL assembly genes in L‐G6pc +/+ and L‐G6pc −/− mice treated with either shChREBP or shSCR (n = 7‐9). (B) Box‐and‐whisker plots presenting hepatic relative abundance of VLDL assembly proteins in L‐G6pc +/+ and L‐G6pc −/− mice treated with shChREBP or shSCR (n = 6‐9). (C) Box‐and‐whisker plots presenting hepatic relative mRNA levels of Tm6sf2 in L‐G6pc +/+ and S4048 mice treated with shChREBP or shSCR (n = 6‐7). (D) Schematic presentation of putative ChREBP (Nos. 1‐4, dark grey) and HNF‐4α (DR‐1, light grey) response elements within the murine Tm6sf2 promoter. Box‐and‐whisker plots presenting in vivo ChIP analysis of the putative ChREBP response elements in the hepatic Tm6sf2 promoter in mice treated with shChREBP or shSCR and infused with S4048 or vehicle (n = 5‐7). (E) Box‐and‐whisker plots presenting firefly‐to‐renilla luciferase activities for the murine Tm6sf2 gene reporter after transfection with HNF‐4α, MLX, ChREBPα, and ChREBPβ plasmids (n = 3‐4 independent experiments, each experiment performed in triplicate). (F) Box‐and‐whisker plots presenting in vivo ChIP analysis of the putative ChREBP response elements in the hepatic Tm6sf2 promoter in overnight fasted or fed C57BL/6J mice (n = 5). *P < 0.05, **P < 0.01, ***P < 0.001 indicates significance compared with shSCR for panels A‐D, compared with pcDNA3.1 for panel E and compared with fasted for panel F. ^P < 0.05, ^^P < 0.01, ^^^P < 0.001 indicates significance compared with L‐G6pc +/+ mice for panels A‐D, compared with control for panel E and compared with ChREBP for panel F. #P < 0.05, ##P < 0.01 indicates significance compared with pcDNA3.1 + HNF‐4α for panel E and compared with fasted for panel F. Abbreviations: Apob, apolipoprotein B gene; Apobec, apolipoprotein B mRNA editing enzyme catalytic subunit gene; ChIP, chromatin immunoprecipitation; ChREBP, carbohydrate response element binding protein; DR‐1, down‐regulator of transcription 1 gene; HNF‐4α, hepatocyte nuclear factor 4 alpha; IgG, immunoglobulin G; L‐G6pc −/−, liver‐specific glucose‐6‐phosphatase catalytic subunit knockout; L‐G6pc +/+, liver‐specific glucose‐6‐phosphatase catalytic subunit–sufficient; MLX, Max‐like protein X; Mttp, microsomal triglyceride transfer protein gene; shChREBP, short hairpin ChREBP; shRNA, short hairpin RNA; shSCR, scrambled shRNA; Tm6sf2, transmembrane 6 superfamily member 2 gene; VLDL, very low density lipoprotein.