The Hepatokine Orosomucoid 2 Mediates Beneficial Metabolic Effects of Bile Acids.

Autor:	Lee SH; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju, Korea., Suh JH; Department 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., Heo MJ; Department 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., Choi JM; Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX., Yang Y; Department 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., Jung HJ; Department 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., Gao Z; The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX., Yu Y; The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX., Jung SY; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX., Kolonin MG; The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX., Cox AR; The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX., Hartig SM; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX., Eltzschig HK; Department 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., Ju C; Department 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., Moore DD; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA., Kim KH; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.; Department 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.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2024 May 01; Vol. 73 (5), pp. 701-712.
DOI:	10.2337/db23-0520
Abstrakt:	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 current 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 diet-induced obesity. Contrary to our expectation, under a high-fat diet (HFD), our Orm2 knockout (Orm2-KO) exhibited a lean phenotype compared with C57BL/6J control, partly due to the increased energy expenditure. However, when challenged with a HFD supplemented with cholic acid, Orm2-KO eliminated the antiobesity 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 interferon-γ/STAT1 activities in inguinal white adipose tissue 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 cross talk through ORM2 induction. (© 2024 by the American Diabetes Association.)
Databáze:	MEDLINE
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