Liu Caizhi, Meng Meiyao, Xu Bo, Xu Yuejie, Li Guoqiang, Cao Yuxiang, Wang Dongmei, Qiu Jin, Yu Jian, Xu Lingyan, Ma Xinran, Hu Cheng
Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Diabetes. 2023 Apr 1;72(4):467-482. doi: 10.2337/db22-0585.
The de novo differentiation of hyperplastic adipocytes from adipocyte progenitor cells (APCs) is accompanied by a reduction in adipose tissue fibrosis and inflammation and improvement in insulin sensitivity in obesity and aging. However, the regulators of APC proliferation are poorly understood. Here, we show that fibroblast growth factor 6 (FGF6) acts in an autocrine and/or paracrine manner to control platelet-derived growth factor receptor α-positive APC proliferation via extracellular signal-regulated kinase (ERK) signaling. Specific FGF6 overexpression in inguinal white adipose tissue (iWAT) improved the signs of high-fat diet- or aging-induced adipose hypertrophy and insulin resistance. Conversely, chronic FGF6 expression blockade in iWAT, mediated by a neutralizing antibody or Fgf6 expression deficiency, impaired adipose tissue expansion and glucose tolerance. Overall, our data suggest that FGF6 acts as a proliferative factor for APCs to maintain fat homeostasis and insulin sensitivity.
在肥胖和衰老过程中，脂肪细胞祖细胞（APC）向增生性脂肪细胞的从头分化伴随着脂肪组织纤维化和炎症的减轻以及胰岛素敏感性的改善。然而，人们对APC增殖的调节因子了解甚少。在此，我们表明成纤维细胞生长因子6（FGF6）以自分泌和/或旁分泌方式通过细胞外信号调节激酶（ERK）信号传导来控制血小板衍生生长因子受体α阳性APC的增殖。腹股沟白色脂肪组织（iWAT）中特异性FGF6过表达改善了高脂饮食或衰老诱导的脂肪肥大和胰岛素抵抗的症状。相反，由中和抗体或Fgf6表达缺陷介导的iWAT中慢性FGF6表达阻断损害了脂肪组织扩张和葡萄糖耐量。总体而言，我们的数据表明FGF6作为APC的增殖因子来维持脂肪稳态和胰岛素敏感性。
