Early metabolic remodeling of insulin sensitivity and substrate oxidation with lipoprotein changes at postoperative day 3 after sleeve gastrectomy

Abstract Laparoscopic sleeve gastrectomy (LSG) markedly improves metabolic status early after surgery, before substantial weight loss. However, the concurrent changes in insulin sensitivity, substrate oxidation preference, and lipoprotein subclass profiles at the immediate postoperative period remain incompletely characterized. This prospective, self-controlled pre-post study recruited 41 patients with severe obesity undergoing LSG. Fasting venous blood was collected preoperatively and on postoperative day 3. Clinical biochemical markers were measured, and high-resolution ¹H-NMR metabolomics analysis was performed to quantify serum metabolites and lipoprotein subclasses (VLDL, LDL, HDL) via density gradient analysis. On postoperative day 3, HOMA-IR decreased significantly by 46.6% ( P < 0.001). Metabolomics analysis revealed significant increases in ketone bodies and decreased pyruvate levels, indicating a shift in substrate preference toward fatty acid oxidation. Notable lipoprotein alterations included reduced large VLDL components, increased large buoyant LDL with decreased small dense LDL components, and consistently reduced triglyceride content across all HDL subclasses. In exploratory analyses, the HDL module score was significantly associated with ΔHOMA-IR after adjusting for covariates (partial r = 0.382, p = 0.020). This pilot study characterizes a concurrent metabolic response pattern as early as postoperative day 3 following sleeve gastrectomy, encompassing improved insulin sensitivity, a substrate oxidation shift toward lipid utilization, and comprehensive lipoprotein subclass remodeling. These changes occur before significant weight loss, providing a descriptive characterization of the metabolic response at this early postoperative timepoint.