Aim: When the body's nutrient storage system is exposed to a state of energy excess for a long time, the energy storage exceeds the effective utilization of energy, leading to obesity. At this point, systemic insulin resistance occurs. The ectopic deposition of lipids in the liver and skeletal muscle increases the accumulation of diacylglycerol (DAG) in tissues and the membrane translocation of protein kinase C (PKCs), thereby damaging the insulin signaling pathway and leading to reduced muscle glucose uptake and decreased hepatic glycogen synthesis. Sleeve gastrectomy (SG) improves the metabolic status of individuals with glucose metabolism disorders in a short period of time, which has not been reasonably explained by previous studies. Methods: Forty 8-week-old male wild-type C57BL/6 mice were randomly divided into four groups, with 10 mice in each group: (RC group: mice fed with low-fat diet); (HFD group: mice fed with high-fat diet); (HFD SO group: high-fat diet-fed mice with sleeve gastrectomy surgery control group); (HFD SG group: high-fat diet-fed mice with sleeve gastrectomy surgery group). The effects of SG on hepatic glycolysis, TCA cycle, pentose phosphate pathway, and de novo fatty acid synthesis in mice were detected at the cellular level using 13C6-glucose metabolic flux technology. Results: The HFD group significantly increased the infiltration of monocytes and plasma cells and inflammatory changes in VAT tissue and liver tissue. It is worth noting that SG significantly improves HFD induced VAT and liver tissue inflammatory lesions. Four weeks after SG surgery, fasting blood glucose and fasting insulin levels were significantly reduced, accompanied by a decrease in circulating FFA concentration and Long Chain Acyl CoA levels, indicating that SG improves obesity glucose and lipid metabolism. Reduced mRNA and protein levels of Cd36, DAG1, and PKC ε in liver tissue after SG surgery. Sleeve gastrectomy surgery can improve the expression levels of genes related to glycolysis and TCA cycle metabolism pathways in rodent skeletal muscles. Conclusion: Sleeve gastrectomy surgery reduces the lipid content of food sources in the bloodstream and the membrane translocation of key fatty acid transporter CD36 in liver cells, thereby reducing the content of long-chain fatty acid acyl CoA in tissues, leading to a decrease in the activity of long-chain fatty acid acyl CoA DAG PKCs axis and alleviation of insulin resistance.

Obesity, Sleeve Gastrectomy, Long-chain Fatty Acid Acyl CoA, DAG PKCs Axis, Insulin Resistance