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Adipocyte-Derived Periostin Mediates Glucocorticoid-Induced Hepatosteatosis in Mice

29 Pages Posted: 7 Sep 2019

See all articles by Jian Wan

Jian Wan

affiliation not provided to SSRN

Yi Shan

affiliation not provided to SSRN

Xi Song

affiliation not provided to SSRN

Song Chen

affiliation not provided to SSRN

Xinyuan Lu

affiliation not provided to SSRN

Jie Jin

affiliation not provided to SSRN

Qing Su

Shanghai Jiao Tong University (SJTU) - Xinhua Hospital

Bin Liu

affiliation not provided to SSRN

Wanju Sun

affiliation not provided to SSRN

Bo Li

Shanghai Jiao Tong University (SJTU) - Xinhua Hospital

More...

Abstract

Long-term glucocorticoids (GCs) therapy usually cause many metabolic side effects, including fatty liver, hyperglycemia and insulin resistance. However, the molecular mechanisms contributing to GCs-induced metabolic disorders remain poorly understood. In the present study, we show that treatment of dexamethasone (DEX), a synthetic analog of GCs, led to the accumulation of triglycerides in the livers of mice, but not in the cultured hepatocytes, suggesting that GCs may promote liver steatosis through integrative organ crosstalk mediated by systemic factors. We further show that DEX could upregulate the expression levels of Periostin in white adipose tissues, which in turn induce liver steatosis and hyperglycemia. Both administration of a Periostin-neutralizing antibody and genetic ablation of Periostin largely attenuated DEX-induced hepatic steatosis. Therefore, our findings identify an important role for Periostin in the regulation of GCs-induced negative side effects.

Funding Statement: This study was supported by Project of Clinical Medical Plateau Discipline Construction in Shanghai Pudong New Area (No. PWYgy2018-07) by J.W., the National Natural Science Foundation of China (No. 81500663), the Shanghai Outstanding Young Doctor Training and Funding Program, and the Shanghai Health and Family Planning Commission Outstanding Youth Program by B.L.

Declaration of Interests: The authors stated: "No potential conflict of interest relevant to this article was reported."

Ethics Approval Statement: The animal protocol was reviewed and approved by the animal care committees of Shanghai Pudong New Area People's Hospital and XinHua Hospital.

Keywords: glucocorticoid, Periostin, hepatosteatosis, Adipocyte, hyperglycemia, PPARalpha

Suggested Citation

Wan, Jian and Shan, Yi and Song, Xi and Chen, Song and Lu, Xinyuan and Jin, Jie and Su, Qing and Liu, Bin and Sun, Wanju and Li, Bo, Adipocyte-Derived Periostin Mediates Glucocorticoid-Induced Hepatosteatosis in Mice (August 29, 2019). Available at SSRN: https://ssrn.com/abstract=3445537 or http://dx.doi.org/10.2139/ssrn.3445537

Jian Wan

affiliation not provided to SSRN

Yi Shan

affiliation not provided to SSRN

Xi Song

affiliation not provided to SSRN

Song Chen

affiliation not provided to SSRN

Xinyuan Lu

affiliation not provided to SSRN

Jie Jin

affiliation not provided to SSRN

Qing Su

Shanghai Jiao Tong University (SJTU) - Xinhua Hospital

Shanghai
China

Bin Liu

affiliation not provided to SSRN

Wanju Sun

affiliation not provided to SSRN

Bo Li (Contact Author)

Shanghai Jiao Tong University (SJTU) - Xinhua Hospital

Shanghai
China

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