Abstract
BACKGRUOUND: Sleeve gastrectomy (SG) is an effective and the most commonly performed surgical intervention for obesity. However, detailed studies on the underlying mechanisms, particularly those involving lipid metabolism, remain limited. This study aimed to identify novel pathways associated with the metabolic efficacy of SG by assessing alterations in the serum lipidomic profiles of obese subjects following surgery. METHODS: A prospective study of 50 obese participants undergoing laparoscopic SG was conducted at a tertiary medical center. Serum samples were collected before surgery and 6 months after SG. Lipidomic profiling was performed alongside comprehensive follow-up assessments. Statistical analyses explored lipidomic alterations and their correlations with changes in clinical parameters (Clinical trial registration No. KCT0003527 and KCT0009704). RESULTS: Participants experienced a 25% reduction in body weight 6 months after SG, with a marked reduction (>70%) in hepatic steatosis and insulin resistance, and a 2-fold increase in plasma oxyntomodulin levels. Lipidomic analysis revealed significant molecular shifts in lipid subclasses based on the fatty acyl composition of lipid species, showing a trend toward higher unsaturation and longer carbon chain lengths, as well as metabolic regulation in specific lipid pathways. Key findings included characteristic shifts within triacylglycerols and glycerophospholipids, which were significantly associated with changes in oxyntomodulin levels. Enhanced phosphatidylcholine-to-lysophosphatidylcholine conversion and upregulated ether lipid levels correlated with liver stiffness measures. Metabolic remodeling of sphingolipids-characterized by a decrease in ceramide/sphingomyelin levels and upregulation of the hexosylceramide pathway-emerged as an additional lipidomic signature after SG. CONCLUSION: These findings highlight the complex lipidomic remodeling underlying the metabolic efficacy and therapeutic potential of SG.