Liraglutide suppression of caloric intake competes with the intake-promoting effects of a palatable cafeteria diet, but does not impact food or macronutrient selection

Abstract

Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, is used as a treatment for Type 2 diabetes mellitus 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: laboratory rodent 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 (1mg/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. Our data also show that drug-induced decreases in intake and body weight are not maintained following termination of treatment.

Keywords: Food choice; GLP-1; Roux-en-Y gastric bypass; Taste preference; Weight loss.

Figure 1

Mean ± SE body weight (top) and total caloric intake (bottom) for the duration of the experiment. Shaded line denotes statistical difference (black: group effect; dark grey: day effect; light grey: day x group interaction; p≤ 0.05). Vertical solid lines separate experimental phases. Vertical dashed lines represent dose increments in the Drug Acclimation phase. For total caloric intake, differences between the days at a phase transition within each group are indicated (Liraglutide [*] or Saline [#]; p≤ 0.05). Additional corresponding statistics can be found in Tables 3 and 5. N=6/group.

Figure 2

Mean ± SE change in proportional caloric intake from individual macronutrients and sugar in the cafeteria diet foods during the Cafeteria Diet Drug phase. Shaded line denotes statistical difference (black: group effect; dark grey: day effect; light grey: day x group interaction; p≤ 0.05). Additional corresponding statistics can be found in Table 2. N=6/group.

Figure 3

Mean ± SE change in proportional calories from the cafeteria foods during the Cafeteria Diet Drug phase. Shaded line denotes statistical difference (black: group effect; dark grey: day effect; light grey: day x group interaction; p≤ 0.05). Additional corresponding statistics can be found in Table 3. N=6/group.

Figure 4

Mean ± SE change in proportional caloric intake from individual macronutrients and sugar in the cafeteria diet foods during the Cafeteria Diet No Drug phase. Shaded line denotes statistical difference (black: group effect; dark grey: day effect; light grey: day x group interaction; p≤ 0.05). Additional corresponding statistics can be found in Table 4. N=6/group.

Figure 5

Mean ± SE change in proportional calories from the cafeteria foods during the Cafeteria Diet No Drug phase. Shaded line denotes statistical difference (black: group effect; dark grey: day effect; light grey: day x group interaction; p≤ 0.05). Additional corresponding statistics can be found in Table 5. N=6/group.