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Adipocyte-Derived Periostin Mediates Glucocorticoid-Induced Hepatosteatosis in Mice
29 Pages Posted: 7 Sep 2019
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
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