Hasty, Alyssa H.
Impact of bariatric surgery on resolution of inflammation in adipose tissue
General Research Subject: Obesity
Focus: Adipocytes, Immunology, Insulin Action\Insulin Resistance, Integrated Physiology
Type of Grant: ADA-Ethicon Endo-Surgery/Covidien Research Award in Bariatric Surgery and Diabetes
Project Start Date: July 1, 2011
Project End Date: June 30, 2014
Diabetes Type: Type 2 diabetes
Bariatric surgery (gastric by-pass) remains one of the most effective treatment options for the downstream metabolic consequences of obesity. While it is known that many of the beneficial effects of bariatric surgery occur even before weight loss, the mechanisms for this are not known. We believe that bariatric surgery can directly lead to improvements in adipose tissue function by causing inflammatory pathways to be turned off. In this proposal, we will use a mouse model of bariatric surgery combined with two different genetic modifications to determine the impact of this surgical procedure on adipose tissue inflammation.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
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. In particular, roux-en-Y gastric bypass (RYGB) is one of the most commonly utilized bariatric surgical procedures in the US. One very interesting aspect of RYGB is its nearly immediate impact on glucose tolerance and insulin sensitivity, even at 24 hours post-surgery, long before any weight loss is evident. The mechanism by which this occurs is not known. Altered negative energy balance, neuronal connections between the brain and gut, changes in gastrointestinal hormone secretion, and changes in AT phenotype and function are among some of the possible mechanisms for the beneficial effects of bariatric surgery. This project will analyze the impact of bariatric surgery on adipose tissue homeostasis. To do this, we will use a mouse model of bariatric surgery. We are particularly interested in whether adipose tissue undergoes a process whereby the inflammation present in obesity is resolved leading to proper lipid storage after bariatric surgery. Ultimately, the knowledge regarding mechanisms of how adipose tissue function improves after bariatric surgery will provide insight into non-surgical methods that might be used to improve the metabolic consequences of obesity.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Obesity is tightly linked to increased risk of insulin resistance and diabetes. Currently, the best known treatment for obesity is bariatric surgery. Interestingly, almost immediately after surgery, even before weight loss, insulin sensitivity is improved. There are many different possible explanations for this, and likely a combination of things are responsible. However, our work will focus specifically on adipose tissue function, and how it improves following bariatric surgery.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
It is important for me to be involved in diabetes research because this disorder affects a vast number of the US population. Due to the rise in obesity in the US, the rate of diabetes has increased. This not only affects adults but also children. Therefore it is imperative to identify safe and effective treatments for diabetes. In order to treat this disorder we must understand the development of diabetes and also how bariatric surgery improves insulin resistance.
In what direction do you see the future of diabetes research going?
I think preventing weight gain is one of the best ways to prevent diabetes. This is, of course, very difficult. Thus, we must continue to find ways to combat the metabolic consequences of obesity. In addition to liver and muscle, adipose tissue is likely one of the main instigators of the insulin resistance associated with obesity. As such, it is a perfect tissue for us to target for therapies for insulin resistance. I think basic science research into the physiological consequences of obesity will open up new therapeutic options.
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