Modeling Transmembrane 6 Superfamily Member 2 p.Glu167Lys-associated Steatotic Liver Disease Using Androgen-treated Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells

We report an improved human hepatocyte differentiation model to investigate metabolic dysfunction with functional VLDL secretory profiles influenced by TM6SF2 gene variant. Our combinatorial analysis of <i>in vitro</i> and human data indicates that male testosterone modifies the effect of E167K on hepatic steatosis but not insulin sensitivity. These data support the hypothesis that male-predominant T2D in E167K carriers is not causative but rather a consequence of persistent steatosis.