Evaluating the gut hormone response following bariatric surgery and in response to oral bile acids

Abstract

Obesity is a global disease and is responsible for a great deal of morbidity and mortality across the world. Bariatric surgery is currently the most effective treatment for obesity, and is also highly effective at treating obesity-associated type 2 diabetes. Bariatric surgery’s beneficial effects are mediated by gut hormones such as Glucagon-Like Peptide-1 (GLP-1), Oxyntomodulin (OXM) and Peptide YY (PYY), and bile acids. These mediators regulate metabolism, increase satiety, and reduce appetite, and increase energy expenditure leading to weight loss. In this thesis, I have investigated the acute effect of two bile acids, Ursodeoxycholic acid (UDCA) and Chenodeoxycholic acid (CDCA), on glucose and gut hormones on healthy volunteers following a meal. CDCA has shown to augment postprandial secretion of gut hormones, while GLP-1 and OXM were also increased in the fasting state. This was also reflected on increasing insulin sensitivity after a meal. These results can play a vital role in better understanding and developing a new treatment for obesity and/or diabetes. My second study focused on understanding the aetiology of poor response to bariatric surgery. By measuring the level of gut hormones (GLP-1, OXM and PYY, termed ‘GOP”) following a meal and the measuring the sensitivity of post bariatric patients to the action of a subcutaneous gut hormone infusion, I aimed to differentiate between good or poor response in these patients. I did not see a significant difference in gut hormones secretions between responders and non-responders, but infusion of GOP or GLP-1 infusions reduced the glucose level in both groups and insulin was attenuated with GOP infusion only. However, both groups did not show any difference in level of energy expenditure, satiety, or food intake. These findings will need further investigation to understand better the role of bile acids and gut hormones in tackling obesity, and the development of pharmacological treatments for obesity.