Potential Involvement of GPR119 Receptor in the Effects of Novel Fat Sensor OEA on Taste Preferences and Body Weight Regulation to High-Fat Diets
Open Access
- Author:
- Jamis, Catherine
- Graduate Program:
- Anatomy
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- March 14, 2016
- Committee Members:
- Andras Hajnal, Thesis Advisor/Co-Advisor
Patricia J Mc Laughlin, Thesis Advisor/Co-Advisor
Kirsteen Nairn Browning, Thesis Advisor/Co-Advisor - Keywords:
- fat sensing
obesity
dietary fat
taste
mouse models - Abstract:
- Taste preference is very important to food selection and eating habits, which are of relevance to the study of both obesity and reward. GPR119 is a receptor for Oleoylethanolamide (OEA), a fatty-acid signaling molecule, present in the gut and brain of rodents and humans. GPR119 regulates insulin and incretin hormone secretion and the use of agonists of GPR119 have been proposed as therapeutic intervention for treating obesity and diabetes. The objective of this research was to investigate whether GPR119 is involved in OEA’s short-term effects on modulating taste preferences and/or long-term effects of highly palatable diets to induce obesity. Accordingly, the study had two specific aims: 1) to investigate the taste preferences, and 2) feeding behavior of GPR119 knockout (GPR119-/-) mice compared to wild type C57BL/6 mice. Our first study used brief (10-s) and short (5-min) access tests to characterize taste responses in GPR119-/- and determine how OEA affects lipid and sweet preferences in GPR119-/-. Our second study examined the involvement of GPR119 receptor in response the high-caloric diets on caloric efficiency (CE =Δkcal/Δg), caloric intake and weight gain. In the brief and short access preference tests, separate groups of mice (GPR119-/- n = 8, wild type n = 8) were used and presented with Intralipid solution (0.625%, 1.25%, 2.5%, 5%, 10%, or 20%) or sucrose solution (GPR119-/- n = 10, wild type n = 10) at different concentrations (0.1M, 0.3M, 0.6M, 0.9M, 1.2M, 1.5M). Lick responses were measured over one 10-second presentation 80 times during a 20 minute testing session. Lick responses were also measured 20 minutes after 2.5mg/kg, 5mg/kg or 10mg/kg OEA intraperitoneal injection. The short access tests were performed with 5-min free access to two sipper tubes containing water and Intralipid solution or sucrose solution. Four groups of mice were used to measure differences in taste preference of different Intralipid concentrations (GPR119-/- n = 10, wild type n = 10) and different sucrose concentrations (GPR119-/- n = 11, wild type n = 11). Intake was measured over a 5-minute access period where mice had a choice between two sipper tubes of water or Intralipid/ sucrose solution. In Aim 2, the feeding study was performed over 6 weeks, using either standard chow (18% protein, 3.3kcal/g, GPR119-/- n = 6, wild type n =6), or high-carbohydrate chow (56.7% carbohydrate, 4.41kcal/g, GPR119-/- n = 6, wild type n =5), or high-fat chow (34.9% fat, 5.24kcal/g, GPR119-/- n = 7, wild type n = 6). In the brief access tests, there was no difference between GPR119-/- and wild type mice for either sucrose or Intralipid, suggesting that the absence of GPR119 has no effect on taste sensation or preferences. In contrast, the results of the short access taste preference study showed GPR119-/- mice consumed less from the high concentration Intralipid solutions than wild type mice (5% Intralipid, -0.07mL, p<0.05; 10% Intralipid, -0.12mL, p < 0.001; 20% Intralipid, -0.09mL, p < 0.01), whereas we did not observe significant differences between strains for sucrose preferences. In the brief access tests, OEA reduced lick responses for both sucrose and Intralipid in dose-related manner in both the GPR119-/- and wild type mice. The GPR119-/- mice showed a reduced sensitivity to lower dose of OEA (5mg/kg) in reducing lick-responses for higher concentrations of sucrose compared to wild type mice. In the long-term dietary experiment, GPR119-/- mice gained less weight on high-fat chow during the 6-week feeding study (p < 0.01). The cumulative caloric intake of GPR119-/- mice on both high-fat and high-carbohydrate diets was lower than in wild type controls (normal, p < 0.01; high-carbohydrate, p < 0.001; high-fat, p < 0.001). The cumulative CE, a proxy measure for basal metabolic rates, suggested that GPR119-/- mice had a higher metabolic rate (lower caloric efficiency) on the high-fat diet (high-fat, p < 0.05), but not while consuming high-carbohydrate diet. The observation that GPR119-/- mice did not consume as much lipid as wild type at higher concentrations in the short access preference data supports our hypothesis that GPR119 receptor is involved in lipid sensing and the formation of taste preference. Furthermore, the results of the dietary study showing that on high-fat diet GPR119-/- mice initially gained less weight and had an overall lower caloric intake and CE than wild type mice, together with reduced short-term preferences for fat, support the hypothesis that one means by which GP119 may reduce body weight on highly palatable diets is to decrease fat intake through reduced oral preferences. Our finding is novel, and points to taste effects adding to the potential underlying mechanism by which the endogenous ligand, OEA and synthetic GPR119 agonists may curb appetite, in turn could be exploited as a therapeutic target for treating obesity. Future studies are warranted to explore the effects of GPR119 on oral and GI fat signaling in the context of cephalic and post-ingestive signals regulating metabolism and relevant to diabetes.