Transmembrane and coiled-coil domain family 3 gene is a novel target of hepatic peroxisome proliferator-activated receptor γ in fatty liver disease

The peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor abundantly expressed in the nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the mechanism by which PPARγ regulates the transmembrane and coiled-coil domain family 3 (Tmcc3) gene in the liver. We found that TMCC3 is highly expressed in the fatty liver of humans and mice with NAFLD and alcoholic fatty liver disease. Three exon 1 variants (Tmcc3-1a, -1b, and -1c) of mouse Tmcc3 were identified. TMCC3-1B was highly expressed in the fatty liver of type 2 diabetic ob/ob mice; however, this increase in expression was ameliorated by liver-specific knockout of PPARγ. Reporter assays and electrophoretic mobility shift assays showed that PPARγ positively regulates Tmcc3-1b and -1c transcription through the same PPARγ-responsive element present in the 5′-region of each Tmcc3. Altogether, our results indicate that Tmcc3 is a novel PPARγ target in the fatty liver disease. [Display omitted] •Tmcc3 is highly expressed in the fatty liver of ob/ob and other mice models.•TMCC3 expression is reduced upon liver-specific PPARγ knockout in ob/ob mice.•PPARγ enhances Tmcc3-1b and -1c expression by binding to the PPAR-response element.•In humans, high TMCC3 expression is associated with NAFLD and AFLD.