Melanie Graham PhD

Project Title: 
How Do Changes in Gut Hormones, Bile Acids and Microbiota Uniquely Provoked by Bariatric Surgery Integrate to Drive Persistent Immune Changes Capable of Improving Insulin Action Independent of Weight Loss

Obesity and related insulin resistance (IR) are major risk factors of type 2 diabetes (T2D), cardiovascular disease, neurodegeneration, and cancer. Bariatric surgery (BS) is currently the most effective treatment for obesity. Prior to significant weight loss, BS improves insulin sensitivity and reverses T2D in a large fraction of patients. Because the cost, adverse events, and non-reversibility of BS limit its applicability, the goal of this research is to clarify the mechanisms that produce the benefits of BS procedures for the purpose of developing non-invasive interventions that harness its key effects.

Obesity links to IR via chronic, low-grade inflammation of subcutaneous and visceral adipose tissues (SAT and VAT), with the VAT being recognized as a site of extensive cellular and molecular crosstalk between the metabolic and immune systems. This group hypothesizes that BS alters gut microbiota-derived metabolites and exosome cargo, which mediate beneficial effects on insulin resistance in large part by modulating the VAT immunologic microenvironment.

Project Investigators

Melanie Graham PhD
Julia Nugent
 
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