Feeding response to mercaptoacetate in Osborne-Mendel and S5B/PL rats

The purpose of this experiment was to determine if Osborne-Mendel (OM) rats, which are susceptible to dietary-induced obesity, and S5B/PL (S5B) rats, which are resistant to dietary-induced obesity, differ in their feeding responses to mercaptoacetate (MA), which blocks fatty acid oxidation, or 2-deoxy-D-glucose (2DG), which blocks glucose utilization. 2DG (100 mg/kg or 200 mg/kg) increased food intake in both strains of rats on a high-fat diet (56% energy from fat). Mercaptoacetate (600 mumol/kg) increased food intake in OM but not S5B rats on a high-fat diet. When maintained on a low-fat diet (10% energy from fat), MA (400 mumol/kg or 600 mumol/kg) stimulated food intake in OM rats, whereas S5B rats increased food intake only after the highest dose of MA (600 mumol/kg). MA stimulated carbohydrate and protein intake in OM rats maintained on a macronutrient selection diet, whereas S5B rats maintained on this diet did not significantly increase intake of any macronutrient after MA. These results demonstrate that OM and S5B rats have a similar food intake response to 2DG but a dissimilar response to MA. The variable response to MA in these strains may be due to a difference in peripheral or central signaling systems related to fatty acid oxidation or a difference in metabolic environments between the strains, which in turn affects the feeding response to MA. These studies suggest that a difference in control of fatty acid oxidation may account for the difference in susceptibility to obesity when eating a high-fat diet.