2,5-anhydro-D-mannitol: a fructose analogue that increases food intake in rats

We examined the effects on food intake and plasma fuels of 2,5-anhydro-D-mannitol (2,5-AM; 2-deoxy-D-fructose), a fructose analogue that inhibits hepatocyte gluconeogenesis and glycogenolysis in vitro. 2,5-AM (50-800 mg/kg po) given to rats during the diurnal fast produced a dose-related increase in food intake during the 2 h after administration. A 200-mg/kg dose of 2,5-AM decreased plasma glucose, increased plasma ketone bodies, free fatty acids, and glycerol, and had no effect on triglycerides. Normal and diabetic rats given 2,5-AM (200 mg/kg ip) increased food intake to the same extent. These results suggest that, unlike other substrate analogues that increase food intake, 2,5-AM increases feeding by creating a metabolic state that resembles fasting.