Sleeve gastrectomy induces adipose browning via suppression of Asprosin and activation of the ATF3-Nrf2/HO-1 axis.
Zhao Shuai, Fu Yayan, Ding Ziwei, Zi Mengli, Wang Jie, Zhou Jiajie, Li Ruiqi, Wang Wei, Wang Daorong
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.
Key Findings
- Sleeve gastrectomy (VSG) induces white adipose tissue (WAT) browning and improves metabolic parameters in obesity and type 2 diabetes mellitus (T2DM).
- VSG suppresses the fasting-induced adipokine Asprosin and activates the ATF3-Nrf2/HO-1 signaling axis, which is linked to thermogenic gene expression.
- Knockdown of Asprosin enhances VSG-induced adipose browning in a HO-1-dependent manner, suggesting a mechanistic role for Asprosin suppression in metabolic improvement.
Clinical Significance
These findings provide mechanistic insight into how sleeve gastrectomy improves metabolism by promoting adipose browning through suppression of Asprosin and activation of the ATF3-Nrf2/HO-1 oxidative stress pathway, highlighting potential therapeutic targets for obesity and T2DM.
Citation
Zhao Shuai, Fu Yayan, Ding Ziweiet al.. Sleeve gastrectomy induces adipose browning via suppression of Asprosin and activation of the ATF3-Nrf2/HO-1 axis. International journal of obesity (2005). 2026-Jul-17.