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Fibroblast growth factor 1 ameliorates adipose tissue inflammation and systemic insulin resistance via enhancing adipocyte mTORC2/Rictor signal.


ABSTRACT: Obesity-induced activation and proliferation of resident macrophages and infiltration of circulating monocytes in adipose tissues contribute to adipose tissue inflammation and insulin resistance. These effects further promote the development of metabolic syndromes, such as type 2 diabetes, which is one of the most prevalent health conditions severely threatening human health worldwide. Our study examined the potential molecular mechanism employed by fibroblast growth factor 1 (FGF1) to improve insulin sensitivity. The leptin receptor-deficient obese mice (db/db) served as an insulin-resistant model. Our results demonstrated that FGF1-induced amelioration of insulin resistance in obese mice was related to the decreased levels of pro-inflammatory adipose tissue macrophages (ATMs) and plasma inflammatory factors. We found that FGF1 enhanced the adipocyte mTORC2/Rictor signalling pathway to inhibit C-C chemokine ligand 2 (CCL2) production, the major cause of circulating monocytes infiltration, activation and proliferation of resident macrophages in adipose tissues. Conversely, these alleviating effects of FGF1 were substantially abrogated in adipocytes with reduced expression of mTORC2/rictor. Furthermore, a model of adipocyte-specific mTORC2/Rictor-knockout (AdRiKO) obese mice was developed to further understand the in vitro result. Altogether, these results demonstrated adipocyte mTORC2/Rictor was a crucial target for FGF1 function on adipose tissue inflammation and insulin sensitivity.

SUBMITTER: Zhao L 

PROVIDER: S-EPMC7687011 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Fibroblast growth factor 1 ameliorates adipose tissue inflammation and systemic insulin resistance via enhancing adipocyte mTORC2/Rictor signal.

Zhao Longwei L   Fan Miaojuan M   Zhao Lijun L   Yun Hongyan H   Yang Yan Y   Wang Chen C   Qin Di D  

Journal of cellular and molecular medicine 20200926 21


Obesity-induced activation and proliferation of resident macrophages and infiltration of circulating monocytes in adipose tissues contribute to adipose tissue inflammation and insulin resistance. These effects further promote the development of metabolic syndromes, such as type 2 diabetes, which is one of the most prevalent health conditions severely threatening human health worldwide. Our study examined the potential molecular mechanism employed by fibroblast growth factor 1 (FGF1) to improve i  ...[more]

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