Background <p>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.</p> Methods <p>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&amp;Tag, and luciferase assays.</p> Results <p>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.</p> Conclusions <p>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.</p> Clinical trial registration <p><a href="https://www.clinicaltrials.gov/">ClinicalTrials.gov</a> identifier NCT07008274.</p>