The hepatokine orosomucoid 2 mediates beneficial metabolic effects of bile acids,Diabetes

当前位置： X-MOL 学术 › Diabetes › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

The hepatokine orosomucoid 2 mediates beneficial metabolic effects of bile acids
Diabetes ( IF 7.7 ) Pub Date : 2024-02-06 , DOI: 10.2337/db23-0520
Sung Ho Lee _{1,

2} , Ji Ho Suh ₃ , Mi Jeong Heo ₃ , Jong Min Choi ₄ , Yang Yang ₃ , Hyun-Jung Jung ₃ , Zhanguo Gao ₅ , Yu Yongmei ₅ , Sung Yun Jung ₆ , Mikhail G. Kolonin ₅ , Aaron R. Cox ₅ , Sean M. Hartig _{1,

7} , Holger K. Eltzschig ₃ , Cynthia Ju ₃ , David D. Moore _{1,

8} , Kang Ho Kim ₁

Affiliation

2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030
3College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju 61186, Korea
1Department of Anesthesiology, Critical Care and Pain Medicine and Center for Perioperative Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030
4Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030
5The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA.
6Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
7Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030
8Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720

Bile acids (BAs) are pleiotropic regulators of metabolism. Elevated levels of hepatic and circulating BAs improve energy metabolism in peripheral organs, but the precise mechanisms underlying the metabolic benefits and harm still need to be fully understood. In the present study, we identified orosomucoid 2 (ORM2) as a liver-secreted hormone (i.e., hepatokine) induced by BAs and investigated its role in BA-induced metabolic improvements in mouse models of dietinduced obesity. Contrary to our expectation, under a high-fat diet (HFD), our Orm2 knockout (Orm2-KO) exhibited a lean phenotype compared to C57BL/6J control, partly due to the increased energy expenditure. However, when challenged with HFD supplemented with cholic acid (HFDCA), Orm2-KO eliminated the anti-obesity effect of BAs, indicating that ORM2 governs BA-induced metabolic improvements. Moreover, hepatic ORM2 overexpression partially replicated BA effects by enhancing insulin sensitivity. Mechanistically, ORM2 suppressed IFNγ/STAT1 activities in inguinal WAT (iWAT) depots, forming the basis for anti-inflammatory effects of BAs and improving glucose homeostasis. In conclusion, our study provides new insights into the molecular mechanisms of BA-induced liver-adipose crosstalk through ORM2 induction.

更新日期：2024-02-06

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>