Source of dietary sucrose influences development of leptin resistance in male and female rats.

Male rats offered 30% sucrose solution in addition to chow develop leptin resistance without an increase in energy intake or body fat. This study tested whether the leptin resistance was dependent on the physical form of the sucrose. Sprague-Dawley rats were offered a sucrose-free (NS) diet, a 66.6% of energy as sucrose (HS) diet, or the NS diet + 30% sucrose solution (LS). Sucrose intake of LS rats equaled that of HS rats, but total carbohydrate intake exceeded that of HS rats. After 33 days, male and female LS rats were resistant to the inhibitory effect of peripherally administered leptin on food intake. LS rats drank small, frequent meals of sucrose during light and dark periods, whereas HS rats consumed more meals during the dark than the light period and remained responsive to leptin. Diet did not affect daily energy intake or insulin sensitivity. There was a small increase in body fat in the female rats. Leptin sensitivity was restored within 5 days of withdrawal from sucrose in male LS rats. This rapid reversal suggested that leptin resistance was associated with the metabolic impact of drinking sucrose. An experiment was carried out to test whether activity of the hexosamine biosynthetic pathway and glycation of leptin signaling proteins were increased in LS rats, but the results were equivocal. A final experiment determined that female LS rats were leptin-resistant within 18 days of access to sucrose solution and that the small, but significant, increase in body fat was associated with increased adipocyte glucose utilization and insulin responsiveness, which may have been secondary to adipocyte leptin resistance.