Sleeve gastrectomy induces adipose browning via suppression of Asprosin and activation of the ATF3-Nrf2/HO-1 axis.

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

International Journal of Obesity Pub Date : 2026-07-17 DOI:10.1038/s41366-026-02167-3

Shuai Zhao, Yayan Fu, Ziwei Ding, Mengli Zi, Jie Wang, Jiajie Zhou, Ruiqi Li, Wei Wang, Daorong Wang

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引用次数: 0

Abstract

Background: Vertical sleeve gastrectomy (VSG) produces rapid metabolic improvement in obesity and type 2 diabetes mellitus (T2DM), yet the molecular basis linking surgery to adipose remodeling remains unclear. The fasting-induced adipokine Asprosin is implicated in metabolic dysregulation, but its role in white adipose tissue (WAT) browning after VSG is unknown.

Methods: Asprosin expression was assessed in human adipose tissues and longitudinally after VSG. A high-fat diet/streptozotocin-induced rat model with obesity and diabetes and differentiated 3T3-L1 adipocytes were used for in vivo and in vitro mechanistic studies, including AAV-mediated knockdown, pharmacological inhibition, CUT&Tag, and luciferase assays.

Results: Asprosin was elevated in obesity and reduced after VSG. In rats, VSG improved metabolic parameters and promoted WAT browning, accompanied by suppression of Asprosin and activation of ATF3-Nrf2/HO-1 signaling. Mechanistically, ATF3 was associated with increased Nrf2 promoter activity and appears to contribute to Asprosin-dependent regulation of thermogenic gene expression. Asprosin knockdown enhanced VSG-induced browning in a HO-1-dependent manner. These findings suggest a potential link between Asprosin suppression and activation of the ATF3-Nrf2/HO-1 axis during VSG-induced adipose browning.

Conclusions: VSG is associated with WAT browning, which may involve suppression of Asprosin and activation of the ATF3-Nrf2/HO-1 axis, providing mechanistic insight into metabolic improvement after bariatric surgery.

Clinical trial registration: ClinicalTrials.gov identifier NCT07008274.

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袖式胃切除术通过抑制Asprosin和激活ATF3-Nrf2/HO-1轴诱导脂肪褐变。

背景：垂直袖胃切除术（VSG）可以快速改善肥胖和2型糖尿病（T2DM）的代谢，但将手术与脂肪重塑联系起来的分子基础尚不清楚。禁食诱导的脂肪因子Asprosin与代谢失调有关，但其在VSG后白色脂肪组织（WAT）褐变中的作用尚不清楚。方法：测定VSG后人脂肪组织和纵向组织中Asprosin的表达。采用高脂肪饮食/链脲霉素诱导的肥胖和糖尿病大鼠模型和分化的3T3-L1脂肪细胞进行体内和体外机制研究，包括aav介导的敲除、药理抑制、CUT&Tag和荧光素酶检测。结果：Asprosin在肥胖组升高，VSG后降低。在大鼠中，VSG改善代谢参数，促进WAT褐变，同时抑制Asprosin和激活ATF3-Nrf2/HO-1信号。从机制上讲，ATF3与Nrf2启动子活性增加有关，似乎有助于asprosin依赖性的产热基因表达调节。Asprosin敲低以ho -1依赖的方式增强vsg诱导的褐变。这些发现表明，在vsg诱导的脂肪褐变过程中，Asprosin抑制与ATF3-Nrf2/HO-1轴的激活之间存在潜在的联系。结论：VSG与WAT褐变有关，这可能涉及Asprosin的抑制和ATF3-Nrf2/HO-1轴的激活，为减肥手术后代谢改善提供了机制见解。临床试验注册：ClinicalTrials.gov识别码NCT07008274。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Obesity 医学-内分泌学与代谢

CiteScore

10.00

自引率

2.00%

发文量

221

审稿时长

3 months

期刊介绍： The International Journal of Obesity is a multi-disciplinary forum for research describing basic, clinical and applied studies in biochemistry, physiology, genetics and nutrition, molecular, metabolic, psychological and epidemiological aspects of obesity and related disorders. We publish a range of content types including original research articles, technical reports, reviews, correspondence and brief communications that elaborate on significant advances in the field and cover topical issues.