Obestatin reduces food intake and suppresses body weight gain in rodents.

Obestatin was recently described as a bioactive peptide encoded for by the same gene as ghrelin but with opposite actions on food intake. Although some groups have confirmed these findings others find no effect. We investigated the effect of obestatin on feeding in rodents over a wide range of doses. Acute administration of obestatin inhibited feeding at doses of 10-100 nmol/kg i.p. in mice and 100-300 nmol/kg i.p. in lean and Zucker fatty rats. Interestingly, the dose-response relationship was U-shaped such that both low and high doses were without effect in either species. Treatment of mice with obestatin over a 7-day period decreased body weight gain and food consumption. Overall, obestatin suppressed food intake and body weight gain in rodent and an unusual dose-response relationship was found. These findings may explain the difficulties in reproducing the effects of obestatin on feeding reported by some groups.