1952-P: Vertical Sleeve Gastrectomy Induces Distinctive Gene Expression Changes in Glucose-Utilizing Peripheral Organs

Abstract

Vertical sleeve gastrectomy (VSG) improves hyperglycemia and can achieve high rate of diabetes remission. To elucidate the molecular mechanism of VSG, we performed transcriptomic analysis of liver, fat, and muscle tissues in VSG mice compared to both sham and pair-fed sham controls. C57BL/6 mice fed high fat diet were randomly assigned to sham or VSG surgery. Sham-operated mice were fed ad libitum (Sham group) or pair-fed (Sham-PF group) matching their food intake to VSG-operated mice. Body weight, food intake, glucose and insulin tolerance were measured. Comparative transcriptomic analysis of liver, epididymal fat, and soleus muscle using RNA sequencing was performed. VSG decreased body weight and maintained the reduced body weight during the whole study period (up to 8 weeks after surgery). However, food intake was only reduced during the first 2 weeks after surgery in VSG than sham group. Glucose tolerance was improved by VSG after oral glucose load, but this improvement was attenuated after intraperitoneal glucose load. In addition, VSG increased insulin sensitivity than both Sham and Sham-PF group. Clustering and principal component analysis of the gene expression profiles of liver and adipose tissue revealed that Sham-PF was closer to Sham than VSG. The number of DEG was larger in comparison between VSG vs. Sham-PF than that between Sham-PF vs. Sham. The gene expression profile of muscle was not distinctive among the three groups. In pathway analysis, immune response was the common pathway enriched in all three tissues of VSG compared to Sham-PF. These results suggest that VSG induces organ specific changes of gene expression profile in both weight-loss dependent and independent ways. Interestingly, weight-loss independent changes were more robust than weight-loss dependent changes, which suggests that the improvement of hyperglycemia may be induced not only by weight-loss dependent mechanisms, but also by weight-loss independent mechanisms of VSG. Disclosure C. Ahn: None. S. Moon: None. Y. Cho: None. Funding Korean Ministry of Health and Welfare (HI14C1277)