Liraglutide-Induced Intake Suppression Competes with an Intake Promoting Cafeteria Diet, but Has No Effect on Relative Intake of Specific Foods or Macronutrients

Liraglutide, a Glucagon-Like Peptide 1 (GLP-1) receptor agonist, is used as a treatment for Type 2 Diabetes Mellitus (T2DM) and obesity because it improves glycemia and decreases food intake. Here, we tested whether chronic activation of the GLP-1 receptor system with liraglutide would induce decreases in intake accompanied by changes in proportional food or macronutrient intake similar to those seen following RYGB in rats when a variety of palatable food options are available. A "cafeteria diet" was used that included: chow, refried beans (low-fat/low-sugar), low-fat yogurt (low-fat/high-sugar), peanut butter (high-fat/low-sugar) and sugar-fat whip (high-fat/high-sugar). Liraglutide (1 mg/kg daily, sc, n=6) induced significant reductions in body weight and total caloric intake compared to saline–injected control rats (n=6). Although access to a cafeteria diet induced increases in caloric intake in both groups relative to chow alone, liraglutide still effectively decreased intake compared with saline-injected rats suggesting that chronic GLP-1 activation competes with the energy density and palatability of available food options in modulating ingestive behavior. Even with the substantial effects on overall intake, liraglutide did not change food choice or relative macronutrient intake when compared to pre-treatment baseline. When drug treatment was discontinued, the liraglutide group increased caloric intake and rapidly gained body weight to match that of the saline group. These results demonstrate that, while liraglutide effectively decreases caloric intake and body weight in rats, it does not cause adjustments in relative macronutrient consumption, suggesting that such changes seen after RYGB are unlikely due to activation of the GLP-1 receptor system alone.