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<p>Actin dynamics, mediated by various actin-binding proteins, plays an important role in adipocyte differentiation. We investigated the role of coactosin-like F-actin binding protein (Cotl1) in adipocyte differentiation in vitro and in vivo. Cotl1 expression level was increased during adipocyte differentiation in mouse 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) and during weight gain in adipose tissues. However, <i>Cotl1</i> deficient in 3T3-L1 and ADSCs inhibited adipocyte differentiation, and <i>Cotl1</i><sup>−/−</sup> mice displayed resistance to high-fat diet (HFD)-induced weight gain, hepatic steatosis and adipocyte enlargement compared to HFD-fed wild type (WT) mice. Ingenuity Pathway Analysis of RNA-sequencing in adipose tissues of HFD-WT and HFD-<i>Cotl1</i><sup>−/−</sup> mice predicted complicated relationships between Cotl1, differentiation of adipocytes, obesity and organization of actin cytoskeleton. Particularly, peroxisome proliferator-activated receptor gamma (<i>Pparg</i>) emerged as a central player, with Cotl1 influencing <i>Pparg</i> expression, consequently regulating adipocyte differentiation. These findings suggest Cotl1 as a pivotal regulator of terminal adipocyte differentiation by modulating adipogenic genes.</p>

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Coactosin-like F-actin binding protein (Cotl1) plays a key role in adipocyte differentiation and obesity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月17日

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  • Eunkuk Park,
  • Hyoju Jeon,
  • Kang-Il Oh,
  • Junhwan Jeong,
  • Do-Wan Kim,
  • Hyun-Seok Jin,
  • Seon-Yong Jeong

摘要

Actin dynamics, mediated by various actin-binding proteins, plays an important role in adipocyte differentiation. We investigated the role of coactosin-like F-actin binding protein (Cotl1) in adipocyte differentiation in vitro and in vivo. Cotl1 expression level was increased during adipocyte differentiation in mouse 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) and during weight gain in adipose tissues. However, Cotl1 deficient in 3T3-L1 and ADSCs inhibited adipocyte differentiation, and Cotl1−/− mice displayed resistance to high-fat diet (HFD)-induced weight gain, hepatic steatosis and adipocyte enlargement compared to HFD-fed wild type (WT) mice. Ingenuity Pathway Analysis of RNA-sequencing in adipose tissues of HFD-WT and HFD-Cotl1−/− mice predicted complicated relationships between Cotl1, differentiation of adipocytes, obesity and organization of actin cytoskeleton. Particularly, peroxisome proliferator-activated receptor gamma (Pparg) emerged as a central player, with Cotl1 influencing Pparg expression, consequently regulating adipocyte differentiation. These findings suggest Cotl1 as a pivotal regulator of terminal adipocyte differentiation by modulating adipogenic genes.