Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Demonstration Center for Experimental Basic Medicine Education, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
Int J Biochem Cell Biol. 2024 Oct;175:106638. doi: 10.1016/j.biocel.2024.106638. Epub 2024 Aug 22.
Obesity is one of the threats to human health and survival. High fat diet (HFD)-induced obesity leads to adipose tissue fibrosis and a series of metabolic diseases. There are some people still thin under HFD, a phenomenon known as the "obesity resistance (OR) phenotype". It was found that Iroquois homeobox 3 (IRX3) is considered as a regulator in obesity, but the regulatory mechanism between OR and IRX3 is still unclear. In this study, we investigated OR on a HFD and the role of the IRX3 gene. Using mice, we observed that OR mice had lower body weights, reduced liver lipid synthesis, and increased white adipose tissue (WAT) lipolysis compared to obesity-prone (OP) mice. Additionally, OR mice exhibited spontaneous WAT browning and less fibrosis, correlating with higher Irx3 expression. Utilizing 3T3-L1 differentiated adipocytes, our study demonstrated that overexpression of Irx3 promoted thermogenesis-related gene expression and reduced adipocyte fibrosis. Therefore, Irx3 promotes WAT browning and inhibits fibrosis in OR mice. These results provide insight into the differences between obesity and OR, new perspectives on obesity treatment, and guidance for lessening adipose tissue fibrosis.
肥胖是威胁人类健康和生存的因素之一。高脂肪饮食（HFD）诱导的肥胖会导致脂肪组织纤维化和一系列代谢疾病。然而，有些人在 HFD 下仍然保持苗条，这种现象被称为“肥胖抵抗（OR）表型”。已经发现同源异型盒基因 3（IRX3）被认为是肥胖的调节剂，但 OR 和 IRX3 之间的调节机制尚不清楚。在这项研究中，我们研究了 HFD 下的 OR 以及 IRX3 基因的作用。使用小鼠，我们观察到与肥胖易感性（OP）小鼠相比，OR 小鼠的体重较低，肝脏脂质合成减少，白色脂肪组织（WAT）脂解增加。此外，OR 小鼠表现出自发性 WAT 褐变和较少的纤维化，与更高的 Irx3 表达相关。利用 3T3-L1 分化的脂肪细胞，我们的研究表明，Irx3 的过表达促进了与产热相关的基因表达，并减少了脂肪细胞纤维化。因此，Irx3 促进了 OR 小鼠的 WAT 褐变和抑制了纤维化。这些结果提供了肥胖和 OR 之间差异的见解，为肥胖治疗提供了新的视角，并为减轻脂肪组织纤维化提供了指导。
