| Autor: |
Lee, Sung Ho, Suh, Ji Ho, Heo, Mi Jeong, Choi, Jong Min, Yang, Yang, Jung, Hyun-Jung, Gao, Zhanguo, Yu, Yongmei, Jung, Sung Yun, Kolonin, Mikhail G., Cox, Aaron R., Hartig, Sean M., Eltzschig, Holger K., Ju, Cynthia, Moore, David D., Kim, Kang Ho |
| Předmět: |
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| Zdroj: |
Diabetes; May2024, Vol. 73 Issue 5, p701-712, 12p |
| 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. Article Highlights: The hepatokine orosomucoid 2 (ORM2) is induced by bile acid overload in the liver as well as by metabolic interventions such as bariatric surgery and calorie restriction. ORM2 is essential for bile acid–induced metabolic improvements in obesity. ORM2 directly targets adipose tissue inflammation to exhibit metabolic benefits. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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