Title: US-Ireland R&D Partnership: Translational Analyses of Ingestive Behavior After Gastric Bypass
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: After Roux-en-Y gastric bypass (RYGB), patients decrease: appetite, caloric intake, body weight, and glycemia which is maintained long-term. It is controversial whether patients shift their preferences from high fat and sugary foods to fruits and vegetables, which, if true, could conceivably contribute to weight loss and improved glycemia. Studies on food selection and intake, however are dominated by measures of verbal report such as dietary recall. Our view is that disparities in the literature could be more effectively resolved by complementing existing findings with direct measures of target behaviors in humans that can also be applied to our animal model and vice-versa. There has been virtually no published work involving direct measures of changes in food selection after RYGB in humans, and the few studies involving animal models have had limited scope. Our first objective with this unique US-Ireland R&D Partnership Program is to extend the findings from our ongoing collaboration suggesting that rats, and perhaps humans, have alterations in food preferences without ostensible changes in food palatability. Although we found some evidence of a reduction in appetitive behavior in humans for candy but not vegetables after RYGB, the support for such changes in rodent models is mixed. Thus, it remains unclear whether there are fundamental shifts in the palatability of high fat and sugary foods or simply a decrease in the motivation to ingest them. Moreover, the changes in food preferences appear to progress with experience implicating learning processes. At issue, is whether food preference modulation after RYGB is due to a fundamental shift in the palatability of such taste stimuli (e.g., conditioned taste aversion), or to learned adjustments in feeding behavior that minimize negative visceral signals during meals (i.e., conditioned avoidance). Such changes in food selection alone have been postulated to benefit patients with Type 2 diabetes mellitus (T2DM) and this may be an under-investigated mechanism by which RYGB improves glycemic control. Understanding the mechanisms of these effects could allow us to improve the perisurgical management of RYGB patients and potentially refine nonsurgical interventions of patients with T2DM and obesity. We propose to use rodents and humans after RYGB to directly measure the selection and intake of foods varying in their fat content and glycemic index, while characterizing the pattern of ingestion within and across meals. The mechanisms underlying changes in feeding, weight loss, and glycemic control remain contested. The most promising lead has come from the observation of an exaggerated pleiotropic gut hormone response to RYGB. We have shown that when this response to food is attenuated by Octreotide (a somatostatin analogue), the size of a fatty and sugary meal increases. Therefore, we have chosen to test the effect of Octreotide on food selection after RYGB in rats and humans. While the apparent progressive changes in food preference after RYGB strongly suggest learning, this may be driven by either food aversion (changed palatability) or food avoidance (unchanged palatability). The evidence disambiguating these learning processes is lacking and we aim to explicitly distinguish between these important and conceptually distinct mechanisms. Thus our specific aims are: 1. Using a nondiabetic and diabetic rat model, we will test the hypothesis that RYGB causes shifts in food selection from high fat (HF) and high glycemic index (HGI) items to low fat (LF) and low glycemic index (LGI) items and alters feeding patterns reducing body weight and blood glucose. We will also test if the expression of such changes in ingestive behavior is dependent on gut peptide responses. 2. Using our rat model, we will test the hypothesis that the progressive decrease in preference for fatty foods after RYGB is not due to a fundamental shift in the palatability of such taste stimuli (i.e., conditioned taste aversion), but rather represents learned adjustments in feeding behavior that minimize negative visceral signals during meals (i.e., conditioned avoidance). We will also test if the progressive changes in ingestive behavior are dependent on exaggerated gut peptide responses and whether similar changes are seen with isocaloric solutions of sugar and sugar+fat mixtures. 3. IRISH COMPONENT: In translational experimental designs guided from Aim 1, we will test the hypothesis that RYGB in humans causes shifts in food selection from HF and HGI items to LF and LGI items and alters feeding patterns reducing body weight and blood glucose. We will also test if the expression of such changes in ingestive behavior is dependent on gut peptide responses.


Research activity codes: 5.4 SURGERY
Health categories: STROKE;ORAL AND GASTROINTESTINAL;METABOLIC AND ENDOCRINE;CARDIOVASCULAR;CANCER AND NEOPLASMS