Development of leptin resistance in sucrose drinking rats is associated with consuming carbohydrate-containing solutions and not calorie-free sweet solution.

Rats offered 30% sucrose solution plus chow or a sucrose-free diet develop leptin resistance within 4 weeks. This experiment tested whether leptin resistance was associated with the reward of sweet taste or the pre- or post-absorptive effects of consumption of simple carbohydrate. Male Sprague Dawley rats were offered a sucrose-free diet (NS), a diet containing 67% calories as sucrose (HS) or NS diet plus 30% sucrose (LS), 0.03% saccharin (Sacc) or 20% SolCarb® solution for 38 days. SolCarb® is a maltodextrin powder. Sacc rats initially drank more than LS rats, but intakes were the same after Day 20. SolCarb® and LS rats drank the same number of calories from Day 15 to the end of the experiment. SolCarb® and LS rats ate less dry food than other groups, but total energy intake was greater than that of NS, HS and Sacc groups and over 80% of their energy intake was from carbohydrate. Leptin responsiveness was tested on Days 27 and 32 with each rat acting as its own control. An i.p. injection of 2 mg/kg leptin inhibited food intake of NS, HS and Sacc rats, but had no effect on energy intake of LS or SolCarb® rats or on consumption of Sacc, sucrose or SolCarb® solution. At the end of the experiment all of the rats were insulin sensitive, had the same body composition and serum leptin concentrations. These data indicate that consumption of a calorie containing carbohydrate solution and not sweet taste drives the development of leptin resistance and suggest that there is lower threshold for inhibition of hunger than for inhibition of reward by leptin.