{"title":"Transmembrane and coiled-coil domain family 3 gene is a novel target of hepatic peroxisome proliferator-activated receptor γ in fatty liver disease","authors":"Daisuke Aibara, Ai Sakaguchi, Kimihiko Matsusue","doi":"10.1016/j.mce.2024.112379","DOIUrl":null,"url":null,"abstract":"<div><div>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 (<em>Tmcc3</em>) 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 (<em>Tmcc3-1a</em>, -<em>1b</em>, and -<em>1c</em>) of mouse <em>Tmcc3</em> were identified. TMCC3-1B was highly expressed in the fatty liver of type 2 diabetic <em>ob/ob</em> 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 <em>Tmcc3-1b</em> and <em>-1c</em> transcription through the same PPARγ-responsive element present in the 5′-region of each <em>Tmcc3</em>. Altogether, our results indicate that <em>Tmcc3</em> is a novel PPARγ target in the fatty liver disease.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"594 ","pages":"Article 112379"},"PeriodicalIF":3.8000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0303720724002351","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.