Differential Regulation of Plasma Obestatin and Ghrelin by Meal Intake and the Cholinergic System in Lean, But Not Obese Individuals

Abstract

Obestatin is cosecreted with and stemming from the same precursor as ghrelin and is apparently involved in energy metabolism. Relatively little is known about the regulation of obestatin release. The regulation of obestatin release and obestatin-to-ghrelin ratios by meal intake and the cholinergic system were studied in lean and obese subjects. We conducted a randomized, double-blind, placebo-controlled, crossover study with 4 study days in eight obese (body mass index >30 kg/m(2)) and eight matched lean (body mass index <25 kg/m(2)) healthy subjects (two males and six females per group) at a University Clinical Research Unit. Atropine (1 mg iv) was administered alone and in combination with breakfast (550 kcal) intake, or placebo (isotonic saline) alone and in combination with breakfast. We measured plasma obestatin and obestatin/ghrelin ratios. Both obestatin and ghrelin/obestatin ratios decreased significantly from baseline by either atropine or meal intake in lean individuals, with the two effects adding up on the combined atropine/breakfast day. In contrast, there were no statistically significant differences in obese subjects, who also showed significantly greater association between ghrelin and obestatin values than their lean counterparts. Obestatin and ghrelin release is differentially regulated by meal intake and the cholinergic system in lean individuals. This regulation is impaired in obesity.