Fibroblast growth factor 6 promotes adipocyte progenitor cell proliferation for adipose tissue homeostasis
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posted on 2023-01-06, 14:52 authored by Caizhi Liu, Meiyao Meng, Bo Xu, Yuejie Xu, Guoqiang Li, Yuxiang Cao, Dongmei Wang, Jin Qiu, Jian Yu, Lingyan Xu, Xinran Ma, Cheng Hu<p>The <em>de</em> <em>novo</em> differentiation of hyperplastic adipocytes from adipocyte progenitor cells (APCs) is accompanied by the reduction of 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) secreted by adipocytes controls PDGFRa+ 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 <em>Fgf6</em> 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.</p>
Funding
The current study was supported by grants from the National Key Research and Development Project of China (2018YFA0800402, 2019YFA0904500), the National Natural Science Foundation of China (81900766, 81974118, 32022034 and 32071148), Shanghai Outstanding Academic Leaders (20XD1433300), and Shuguang Project (21SG11), and Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212700).
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