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Biochem Biophys Res Commun. 2019 Mar 26;511(1):73-78. doi: 10.1016/j.bbrc.2019.02.037. Epub 2019 Feb 13.

Genetic deletion of β2 adrenergic receptors exacerbates hepatocellular lipid accumulation in high-fat diet mice.

Author information

1
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China; Clinical Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.
2
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
3
Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China; Clinical Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China. Electronic address: qs_tong@hotmail.com.
4
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan, 430030, China. Electronic address: fuqin@mails.tjmu.edu.cn.

Abstract

β2 Adrenergic receptors (β2ARs) are G protein-coupled receptors (GPCRs) that are expressed in major insulin target tissues. β2ARs play an important role in the regulation of lipid metabolism during aging; however, little is known about the significance of β2ARs in the pathogenesis of hepatic fat accumulation in high-fat diet (HFD) mice. This study aims to examine the role of β2AR in the development of nonalcoholic fatty liver disease (NAFLD) induced by HFD and the underlying mechanisms. Surprisingly, we found that genetic deletion of β2AR significantly increased the liver weight of mice fed a HFD for 20 weeks compared to that of wild-type (WT) mice. Moreover, genetic deletion of β2AR could aggravate HFD-induced liver lipid accumulation and liver injury in mice. Mechanistically, we demonstrated that β2AR deletion significantly activated PPARγ/CD36 signaling via inactivation of the cAMP response element-binding (CREB) protein to facilitate hepatocellular lipid deposition in HFD mice. Together, our results identify β2AR as a plausible therapeutic target for preventing or treating NAFLD.

KEYWORDS:

Fatty acid metabolism; High-fat diet; Nonalcoholic fatty liver; β(2) adrenergic receptor

PMID:
30770098
DOI:
10.1016/j.bbrc.2019.02.037

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