2-Deoxy-D-glucose and mercaptoacetate induce different patterns of macronutrient ingestion

2-Deoxy-D-glucose (2DG) and mercaptoacetate (MA) are antimetabolic agents that reduce the metabolism of glucose and fatty acids, respectively, and stimulate feeding. The present study compared the effects of MA and 2DG on macronutrient self-selection. Because 2DG and MA have different metabolic actions and appear to activate different neural pathways, our hypothesis was that 2DG and MA would elicit different patterns of macronutrient selection. The first experiment examined macronutrient selection in response to 2DG, MA, and 0.9% saline in rats maintained on a three-macronutrient self-selection diet consisting of cornstarch, casein, and vegetable oil. Subsequently, one macronutrient source was replaced in each of three similar experiments with Polycose, albumin, or solid vegetable shortening. Finally, 2DG and MA tests were conducted in which only one macronutrient (cornstarch, casein, or oil) was available during the test. Results show that MA and 2DG elicit different macronutrient preferences. 2DG elicits intake of all three macronutrients in the same relative proportion consumed during spontaneous feeding across a number of dietary conditions, suggesting that glucoprivation activates interoceptive signals and neural pathways similar to those involved in normal hunger. MA elicits a selective intake of protein. Conditions in which carbohydrate palatability is enhanced or protein palatability is diminished lead to a relative increase in carbohydrate intake in response to MA. However, MA did not increase the intake of fat. Results suggest that intake of each macronutrient is subject to separate neural or endocrine control, and that these controls are linked to metabolic cues.