Zinc alpha2 glycoprotein alleviates palmitic acid-induced intracellular lipid accumulation in hepatocytes. (5th January 2017)

• Record Type: Journal Article
• Authors: Xiao, Xinhua; Li, Han; Qi, Xiaoyan; Wang, Yadi; Xu, Canxin; Liu, Gexin; Wen, Gebo; Liu, Jianghua
• Is Part Of: Molecular and cellular endocrinology. Volume 439(2017)
• Page Start: 155
• Page End: 164
• Publication Date: 2017-01-05
• Subjects: Non-alcoholic fatty liver disease -- Triglycerides -- Fatty acid oxidation -- Lipogenesis -- Nuclear receptors -- Adiponectin; ZAG zinc alpha2 glycoprotein -- NAFLD non-alcoholic fatty liver disease -- TG triglycerides -- PA palmitic acid -- SREBP-1c sterol-regulatory element binding protein 1c -- LXR liver X receptor -- FXR farnesoid X receptor -- PPARα peroxisome proliferator-activated receptor alpha -- FAS fatty acid synthase -- ACC acetyl-CoA carboxylase -- SCD-1 stearoyl-CoA desaturase 1 -- FATP fatty acid transport protein -- CPT-1A carnitine palmitoyltransferase 1A; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.06.003
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Zinc alpha2 glycoprotein (ZAG) plays an important role in stimulating fat mobilization and lipolysis in adipose tissue, but its role in hepatic lipid metabolism remains unclear. Palmitic acid (PA) was used to stimulate HepG2 cells with ZAG overexpression or ZAG knock down (shRNA). Overexpression of ZAG significantly inhibited lipogenesis, promoted lipolysis and fatty acid β-oxidation, and attenuated PA-induced intracellular fat accumulation. Moreover, ZAG overexpression dramatically stimulated adiponectin expression in HepG2 cells. In contrast, knockdown of ZAG notably inhibited fatty acid β-oxidation, increased lipogenesis and lipid accumulation. Collectively, these data suggest that ZAG has the potential to alleviate hepatosteatosis, making it a promising therapeutic target for fatty liver. Highlights: This paper provides the first physiological evidence for the role of Zinc alpha2 glycoprotein (ZAG) in the regulation of lipid metabolism in hepatocytes. Our study has identified, for the first time, manipulation of ZAG expression in hepatocytes altered hepatic TG accumulation and the expression of key fatty acid oxidation genes and lipogenesis genes. ZAG could also dramatically stimulate adiponectin expression in hepatocytes.