Relationships Between Changes in Serum Ketone Body Levels and Metabolic Effects in Patients with Severe Obesity Who Underwent Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Serum ketone bodies increase due to dynamic changes in the lipid metabolisms of patients undergoing bariatric surgery. However, there have been few studies on the role of ketone bodies after bariatric surgery. We aimed to clarify the role of and relationship between the changes in serum ketone bodies and weight loss, as well as between those changes and the metabolic effects after laparoscopic sleeve gastrectomy (LSG). METHODS: We recruited 52 patients with severe obesity who underwent LSG. We measured acetoacetic acid (AcAc) and ß-hydroxybutyric acid (ß-OHB) at the baseline, 1 month, and 6 months after LSG. Subsequently, we compared the changes in the serum ketone bodies with weight-loss effects and various metabolic parameters. RESULTS: At 1 month after LSG, ß-OHB significantly increased (p = 0.009), then significantly decreased 6 months after LSG (p = 0.002). In addition, ß-OHB in patients without Type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH) was notably higher than in patients with T2D at 1 month after LSG (p < 0.001). In the early phase, both AcAc and ß-OHB mainly had strong positive correlations with changes in T2D- and MASH-related parameters. In the middle term after LSG, changes in both AcAc and ß-OHB were positively correlated with changes in lipid parameters and chronic kidney disease-related parameters. CONCLUSION: We demonstrated that the postoperative surge of ketone bodies plays a crucial function in controlling metabolic effects after LSG. These findings suggest the cause- and consequence-related roles of ketone bodies in the metabolic benefits of bariatric surgery.

Effects of laparoscopic sleeve gastrectomy on nonalcoholic fatty liver disease and TGF-ß signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) develops as a result of unhealthy lifestyle but improves with laparoscopic sleeve gastrectomy (LSG). The transforming growth factor (TGF)-ß signaling pathway reportedly contributes to liver fibrosis, mainly in animal experiments. The aim of the present study was to evaluate changes in serum proteins before and after LSG by proteomic analysis and to investigate their association with NAFLD. This study enrolled 36 severely obese patients who underwent LSG at our hospital from January 2020 to April 2022. As a pilot study, proteomic analysis was conducted on six patients using serum collected before and at 6 months after LSG, and significantly fluctuating proteins were extracted. Subsequently, verification by enzyme-linked immunosorbent assay (ELISA) using collected serum was performed on the remaining 30 patients. The mean weight of enrolled patients was 118.5 kg. Proteomic analysis identified 1,912 proteins, many of which were related to the TGF-ß signaling pathway. Among these proteins, we focused on five TGF-ß-related proteins: asporin, EMILIN-1, platelet factor-4, serglycin, and thrombospondin-1. Verification by ELISA revealed that asporin (p = 0.006) and thrombospondin-1 (p = 0.043) levels significantly fluctuated before and after LSG. Univariate analysis with a linear regression model showed that aspartate aminotransferase (p = 0.045), asporin (p = 0.011), and thrombospondin-1 (p = 0.022) levels were significantly associated with postoperative liver fibrosis. On multivariate analysis, asporin was an independent prognostic factor for postoperative liver fibrosis (95% confidence interval: 0.114-1.291, p = 0.002). TGF-ß-related proteins dramatically fluctuated before and after LSG and were correlated with NAFLD pathogenesis. Asporin may be a useful prognostic marker of liver fibrosis in NAFLD after LSG.