Inhibition of the mTORC1 pathway alleviates adipose tissue fibrosis
Sa Gong,
Chang Li,
Qingyang Leng,
Chongxiao Liu,
Yi Zhu,
Hongli Zhang,
Xiaohua Li
Affiliations
Sa Gong
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China; Shanghai Songjiang District Fangta Hospital of Traditional Chinese Medicine, Shanghai, 201600, China
Chang Li
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
Qingyang Leng
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
Chongxiao Liu
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
Yi Zhu
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China
Hongli Zhang
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China; Corresponding author. Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China.
Xiaohua Li
Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China; Corresponding author. Department of Endocrinology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, China.
Background: Adipose fibrosis is a major factor of adipose dysfunction, which causes metabolic dysfunction during obesity, but its molecular mechanisms are poorly understood. This study investigated the role and potential mechanisms of mTORC1 in obesity-induced adipose fibrosis. Methods: ob/ob mice were injected with rapamycin or the same volume of normal saline. The level of fibrosis in epididymal adipose tissue (EAT) was detected by observing aberrant deposition of extracellular matrix. Expression of fibrotic related genes was analysed using RNA-seq. 3T3-L1 preadipocytes were treated with cobalt chloride (CoCl2) and TGF-β1 to induce preadipocyte fibrosis. The fibrosis-related gene expression and protein levels were determined by RT-PCR, WB, and immunofluorescence in two types of fibrotic preadipocytes with or without rapamycin. Results: Compared with vehicle treatment, EAT fibrosis-related aberrant deposition of extracellular matrix proteins and fibrotic gene expression were reduced in ob/ob mice treated with rapamycin. Both CoCl2-induced hypoxia and TGF-β1 successfully promoted adipocyte fibrosis, and the upregulated fibrosis-related genes expression was inhibited after the mTORC1 pathway was inhibited by rapamycin. Conclusion: Inhibition of the mTORC1 pathway ameliorates adipose fibrosis by suppressing fibrosis-related genes in hypoxia- and TGF-β-induced fibrotic preadipocytes.
