Sleeve Gastrectomy Improves Hepatic Glucose Metabolism by Downregulating FBXO2 and Activating the PI3K-AKT Pathway

Abstract

Type 2 diabetes mellitus (T2DM), a chronic metabolic disease, is a public health concern that seriously endangers human health. Sleeve gastrectomy (SG) can relieve T2DM by improving glucose homeostasis and enhancing insulin sensitivity. However, its specific underlying mechanism remains elusive. SG and sham surgery were performed on mice fed a high-fat diet (HFD) for 16 weeks. Lipid metabolism was evaluated via histology and serum lipid analysis. Glucose metabolism was evaluated using the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Compared with the sham group, the SG group displayed a reduction in liver lipid accumulation and glucose intolerance, and western blot analysis revealed that the AMPK and PI3K-AKT pathways were activated. Furthermore, transcription and translation levels of FBXO2 were reduced after SG. After liver-specific overexpression of FBXO2, the improvement in glucose metabolism observed following SG was blunted; however, the remission of fatty liver was not influenced by the over expression of FBXO2. Our study explores the mechanism of SG in relieving T2DM, indicating that FBXO2 is a noninvasive therapeutic target that warrants further investigation.

Sleeve gastrectomy improves cardiac function and glucose-lipid metabolism disorder in obese rats induced by a high-fat and high-sugar diet

“…Moreover, although SG does not directly modify the gastrointestinal structure, changes in hormone levels, improved glucose and lipid metabolism, and altered food preferences following the surgery also lead to changes in the composition of intestinal bacteria. These factors interact with each other and act as causative factors, ultimately leading to postoperative weight loss and improvement in metabolic-related conditions [18,19]. In this study, we observed a significant decrease in body weight during the first two weeks after SG, Endocrine Journal Advance Publication followed by a gradual increase.…”

Flavonoids from Lophatherum gracile Brongn. Ameliorate Liver Damages in High-Fat Diet and Streptozotocin-Induced Diabetic Mice by Regulating PI3K/AKT and NF-Kappa B Pathways

“…A growing number of studies have expounded on how the PI3K/AKT pathway regulates liver functions in T2DM after medication or surgery intervention. For example, both sleeve gastrectomy and c-glutamylcysteine intervention could ameliorate T2DM-induced hepatic injuries through this pathway [28,29]. In this present study, it was noted that the expression of p-PI3K and p-AKT in the liver were signifcantly increased when mice were administrated with LGBF at 17.5 mg/kg for 4 weeks, indicating the positive efects of LGBF on liver metabolism.…”