Tertiary butylhydroquinone alleviated liver steatosis and increased cell survival via β-arrestin-2/PI3K/AKT pathway

Document Type : Original Article


1 College of Pharmacy, Xinxiang Medical University, Xinxiang, China

2 Xinxiang Key Laboratory of Vascular Remodeling Intervention and Molecular Targeted Therapy Drug Development, Xinxiang, China

3 Department of Pharmacy, The first Affiliated Hospital of Xinxiang Medical University, Xinxiang, China

4 Henan International Joint Laboratory of Cardiovascular Remodeling and Drug Intervention, Xinxiang, China

5 School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China, 453003


Objective(s): This study aimed to evaluate the effects and the underlying mechanisms of tertiary butylhydroquinone (TBHQ) on diabetic liver steatosis and cell survival.
Materials and Methods: We performed streptozocin injection and used a high-sugar-high-fat diet for mice to develop an animal model of type 2 diabetes mellitus (T2DM). Bodyweight, blood glucose levels, and content of insulin were measured on all of the mice. The liver tissues were observed by hematoxylin-eosin staining. Protein levels of the liver were measured by Western blot analysis in mice. Primary hepatocytes were induced by hypochlorous acid (HClO) and insulin to form insulin resistance (IR). Primary hepatocyte apoptosis was observed by Hoechst staining. The PI3K/AKT signaling pathway and β-arrestin-2 factor were evaluated by Western blot assay.
Results: TBHQ reduced the blood glucose level and content of insulin in serum, increased body weight, and effectively alleviated liver steatosis in diabetic mice. TBHQ significantly up-regulated the expression of p-PI3K, p-AKT, GLUT4, GSK3β, and β-arrestin-2 in the liver of diabetic mice. Cell experiments confirmed that TBHQ increased the survival ability of primary hepatocytes, and TBHQ improved the expression of p-PI3K, p-AKT, GLUT4, and GSK3β by activating β-arrestin-2 in primary hepatocytes.
Conclusion: TBHQ could alleviate liver steatosis and increase cell survival, and the mechanism is due in part to β-arrestin-2 activation.


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