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.
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.
|Albaugh, Vance L; Banan, Babak; Antoun, Joseph et al. (2018) Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery. Gastroenterology :|
|Albaugh, Vance L; Banan, Babak; Ajouz, Hana et al. (2017) Bile acids and bariatric surgery. Mol Aspects Med 56:75-89|
|Tamboli, Robyn A; Antoun, Joseph; Sidani, Reem M et al. (2017) Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans. Diabetes Obes Metab 19:1267-1275|
|Albaugh, Vance L; Pinzon-Guzman, Carolina; Barbul, Adrian (2017) Arginine-Dual roles as an onconutrient and immunonutrient. J Surg Oncol 115:273-280|
|Albaugh, Vance L; Mukherjee, Kaushik; Barbul, Adrian (2017) Proline Precursors and Collagen Synthesis: Biochemical Challenges of Nutrient Supplementation and Wound Healing. J Nutr 147:2011-2017|
|Tamboli, Robyn A; Sidani, Reem M; Garcia, Anna E et al. (2016) Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans. Am J Physiol Endocrinol Metab 311:E252-9|
|Albaugh, Vance L; Flynn, C Robb; Tamboli, Robyn A et al. (2016) Recent advances in metabolic and bariatric surgery. F1000Res 5:|
|Albaugh, Vance L; Flynn, Charles Robb; Cai, Steven et al. (2015) Early Increases in Bile Acids Post Roux-en-Y Gastric Bypass Are Driven by Insulin-Sensitizing, Secondary Bile Acids. J Clin Endocrinol Metab 100:E1225-33|
|Flynn, Charles Robb; Albaugh, Vance L; Cai, Steven et al. (2015) Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun 6:7715|