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Published on: October 23, 2018
Inhibition of the mTORC1 pathway alleviates adipose tissue fibrosis
Sa Gong1,2, Chang Li1, Qingyang Leng1
1Department 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.
Insights
Inhibition of mTORC1 signaling reduces adipose fibrosis in obesity by suppressing fibrotic genes. This finding offers potential therapeutic targets for metabolic dysfunction associated with obesity.
Area of Science:
- Biochemistry
- Molecular Biology
- Metabolic Research
Background:
- Adipose fibrosis is a key driver of adipose dysfunction and metabolic issues in obesity.
- The precise molecular mechanisms underlying adipose fibrosis remain largely unknown.
- This study focuses on the mechanistic role of mTORC1 in obesity-related adipose fibrosis.
Purpose of the Study:
- To investigate the role of the mTORC1 pathway in obesity-induced adipose fibrosis.
- To elucidate the molecular mechanisms by which mTORC1 influences adipose fibrosis.
- To evaluate the therapeutic potential of mTORC1 inhibition in mitigating adipose fibrosis.
Main Methods:
- Utilized ob/ob mice treated with rapamycin (mTORC1 inhibitor) or saline.
- Assessed epididymal adipose tissue (EAT) fibrosis via extracellular matrix deposition.
- Employed RNA-seq to analyze fibrotic gene expression.
- Induced preadipocyte fibrosis using CoCl2 (hypoxia) and TGF-β1 in 3T3-L1 cells.
- Quantified fibrosis-related gene and protein expression using RT-PCR, Western Blot, and immunofluorescence.
Main Results:
- Rapamycin treatment significantly reduced EAT fibrosis and fibrotic gene expression in ob/ob mice compared to controls.
- CoCl2-induced hypoxia and TGF-β1 effectively promoted adipocyte fibrosis in vitro.
- Inhibition of mTORC1 by rapamycin suppressed the upregulation of fibrosis-related genes in both hypoxia- and TGF-β1-induced fibrotic preadipocytes.
Conclusions:
- Inhibition of the mTORC1 pathway effectively ameliorates adipose fibrosis.
- mTORC1 suppression acts by downregulating the expression of fibrosis-related genes.
- These findings highlight mTORC1 as a critical regulator of adipose fibrosis and a potential therapeutic target for obesity-related metabolic dysfunction.
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