Project description:To investigate the alterations in the jejunal Roux limb lncRNA expression signatures after DJB and analyze the functional pathways associated with metabolic improvement on a genome-wide scale in high-fat diet (HFD)-induced diabetic mice.
Project description:Metabolic and bariatric surgery (MBS) can generate a drastic shift of coding and non-coding RNAs expression pattern, which triggers organ function remodeling and may induce type 2 diabetes (T2D) remission. Our previous studies demonstrated that the altered expression profiles of duodenal and jejunal long noncoding RNAs (lncRNAs) after the duodenal-jejunal bypass (DJB), an investigational procedure and research tool of MBS, can improve glycemic control by modulating entero-pancreatic axis and gut-brain axis, respectively. As an indiscerptible part of intestine, the ileal lncRNAs expression signatures after DJB and the critical pathways associated with postoperative correction of impaired metabolism need to be investigated
Project description:Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a pre-clinical BC model. A potential mechanism of bariatric surgery-associated protection is through the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbial transplant. Cecal contents were isolated from either obese controls that received sham surgery or formerly obese mice following bariatric surgery-induced weight loss and transferred by FMT to lean recipients. Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric-surgery treated mice. Microbes can impact tumor burden through microbially derived metabolites produced or modified by gut microbiota including branched chain amino acids (BCAA). Circulating BCAA correlated significantly with NK T cell content in the tumor microenvironment in both donor mice after bariatric surgery and in FMT recipients of donor cecal content after bariatric surgery compared to obese sham controls. Findings implicate a role of microbially-derived BCAA in activating anti-tumor immunity that is dependent upon bariatric surgery. Importantly, when stool from a patient who exhibited 25% weight loss post-bariatric surgery was transplanted into recipient mice and compared to the patient’s pre-bariatric surgery stool transplant. Patient samples post bariatric surgery significantly reduced tumor burden by 2.4-fold and immunotherapy effectiveness was doubled. Taken together, findings suggest that reinvigorating anti-tumor immunity may be dependent upon microbially derived metabolites such as BCAA.
Project description:The molecular background of mitochondrial dysfunction in adipose tissue of morbidly obese individuals and bariatric surgery-induced changes in adipose mitochondrial function remain incompletely understood. To evaluate the mechanisms behind the surgery-induced changes and differences between morbidly obese subjects and nonobese controls, we performed a LC-MS/MS proteomics analysis of abdominal subcutaneous (SAT) and visceral adipose tissue samples (VAT) collected from the bariatric surgery, SAT samples collected 6 months after surgery, and control SAT and VAT samples collected from baseline.
Project description:Adipose tissue before and after bariatric surgery (BPD/DS)-Pilot study using AB1700 microarrays. Subcutaneous abdominal adipose tissue pre and post bariatric surgery (BPD/DS).
Project description:Evaluate differences in gene methylation levels between offspring born after maternal bariatric surgery and their siblings born before surgery Offspring born after maternal bariatric surgery (AMS, N=25) vs. offspring born before maternal surgery (BMS, N=25)