Shin Min Cheol, Jung Young Hoon, Jeong Yelin, Oh Ah-Reum, Lee Sang Bae, Kim KyeongJin
Department of Biomedical Sciences, College of Medicine, Inha University, Republic of Korea; Program in Biomedical Science & Engineering, Inha University, Republic of Korea; Research Center for Controlling Intercellular Communication (RCIC), College of Medicine, Inha University, Incheon, 22212, Republic of Korea.
Division of Life Sciences, Jeonbuk National University, Jeonju, 54896, Republic of Korea.
Biochem Biophys Res Commun. 2023 Apr 23;653:126-132. doi: 10.1016/j.bbrc.2023.02.068. Epub 2023 Feb 25.
Obesity is commonly associated with excessive adipogenesis, a process by which preadipocytes undergo differentiation into mature adipocytes; however, the mechanisms underlying adipogenesis are not completely understood. Potassium channel tetramerization domain-containing 17 (Kctd17) belongs to the Kctd superfamily and act as a substrate adaptor of the Cullin 3-RING E3 ubiquitin ligase, which is involved in a wide variety of cell functions. However, its function in the adipose tissue remains largely unknown. Here, we found that Kctd17 expression levels were increased in white adipose tissue, especially in adipocytes, in obese mice compared to lean control mice. Gain or loss of function of Kctd17 in preadipocytes inhibited or promoted adipogenesis, respectively. Furthermore, we found that Kctd17 bound to C/EBP homologous protein (Chop) to target it for ubiquitin-mediated degradation, and this process was likely associated with increased adipogenesis. In conclusion, these data suggest that Kctd17 plays an important role in adipogenesis and can be a novel therapeutic target for obesity.
肥胖通常与脂肪生成过多有关，脂肪生成是一个前脂肪细胞分化为成熟脂肪细胞的过程；然而，脂肪生成的潜在机制尚未完全明确。含钾通道四聚化结构域17（Kctd17）属于Kctd超家族，作为Cullin 3-RING E3泛素连接酶的底物衔接子，参与多种细胞功能。然而，其在脂肪组织中的功能仍知之甚少。在此，我们发现与瘦对照小鼠相比，肥胖小鼠白色脂肪组织中，尤其是脂肪细胞中，Kctd17的表达水平升高。前脂肪细胞中Kctd17功能的获得或丧失分别抑制或促进了脂肪生成。此外，我们发现Kctd17与C/EBP同源蛋白（Chop）结合，使其成为泛素介导降解的靶点，这一过程可能与脂肪生成增加有关。总之，这些数据表明Kctd17在脂肪生成中起重要作用，可能成为肥胖症的新型治疗靶点。
