MMPC :: MICROMouse Program Application Abstract

MICROMouse Program Application Abstract

MMPC Funded Abstracts

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Impact of Bariatric Surgery on Adipose Tissue Inflammation

Alyssa Hasty (Nashville, TN)

MICROMouse Program

The past three decades have seen an alarming increase in the prevalence of obesity, which reaches across all ethnic, racial, and socioeconomic backgrounds. In addition to being associated with increased risk of all-cause mortality, obesity is an independent predictor of and diabetes and cardiovascular disease (CVD). The persistent state of subclinical inflammation which characterizes obesity is thought to play an important role in the pathophysiological link between obesity and disease risk. Central to this ‘inflammatory hypothesis’ is the role of adipose tissue macrophages (ATM) in mediating the inflammatory response to chronic over-nutrition. Current therapies for obesity and its associated metabolic pathologies are limited. Despite its many associated issues, bariatric surgery remains the most effective therapy to induce and maintain weight loss. One very interesting results of bariatric surgery in humans is the nearly immediate impact on metabolic parameters, even at 24 hours post-surgery, long before any weight loss is evident. The mechanism by which this occurs is not known, and we hypothesize that altered AT function may contribute to the immediate and long-term beneficial effects of bariatric surgery. It is imperative that we utilize rodent models to determine whether AT inflammation is impacted by bariatric surgery, and whether these changes contribute to the overall beneficial effects of surgery, both before and after actual weight loss. Thus, the overall goal of this proposal is to build on the ongoing characterization of mouse bariatric surgery at Vanderbilt and our earlier work accomplished in conjunction with the Vanderbilt MMPC by determining the impact of bariatric surgery on ATM numbers and inflammatory status, as well as systemic inflammation. . We hypothesize that bariatric surgery can impact ATMs in 2 ways: 1) reducing the inflammatory potential of existing ATMs immediately after surgery, and 2) decreasing the number of ATMs during weight loss after surgery. These hypotheses will combine with experiments characterizing the time course of changes in glucose tolerance, insulin sensitivity, and other adaptations that occur with bariatric surgery that are ongoing in the MMPC.

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