Obesity and diabetes are considered the new worldwide epidemics. It is well accepted that Roux-en-Y gastric bypass (RYGB) surgery is the most effective treatment for obesity and the associated type 2 diabetes. Interestingly, the improvements following RYGB start occurring before weight loss, and the mechanism for these effects is unknown. Recent findings in our laboratory have identified bile acids to be responsible for a significant portion of such metabolic improvements. Our laboratory has been successful in establishing mouse models of RYGB similar to those performed in humans. In an attempt to understand the potential role of bile acids in the metabolic improvements seen with RYGB, we have created a new mouse model that enables diversion of bile acids to various segments of the small intestine without altering the anatomy of the stomach. Our preliminary studies show that biliary diversion to the ileum produces better weight loss and protection from high fat diet-induced obesity than RYGB. These findings suggest that bile acids may be a major signal leading to amelioration of obesity and cure of diabetes after RYGB. This proposal will examine the molecular mechanisms of how bile acid metabolism/kinetics and signaling are altered by biliary diversion to produce more effective and sustained weight loss and resistance to diet- induced obesity compared to RYGB. This work may identify new anti-diabetes and anti-obesity drug targets, but more importantly could identify simpler but more effective surgical treatments for obesity and diabetes.

Public Health Relevance

Obesity and type 2 diabetes are growing health concerns worldwide. Gastric bypass surgery is the only effective treatment for obesity and the only potential cure for type 2 diabetes. Understanding the mechanism of how gastric bypass surgery works to treat and prevent these diseases could lead to better, safer, and more effective therapies for these diseases and is the overarching goal of the proposed research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK103474-01A1
Application #
8836252
Study Section
Special Emphasis Panel (ZDK1-GRB-2 (O1))
Program Officer
Podskalny, Judith M,
Project Start
2014-09-02
Project End
2017-09-01
Budget Start
2014-09-02
Budget End
2015-09-01
Support Year
1
Fiscal Year
2014
Total Cost
$59,544
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212