Differential regulation of plasma obestatin and ghrelin by meal intake and the cholinergic system in lean, but not obese individuals

Abstract

Context: 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.

Objective: The regulation of obestatin release and obestatin-to-ghrelin ratios by meal intake and the cholinergic system were studied in lean and obese subjects.

Design, participants, and setting: 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.

Interventions: 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.

Main outcome measures: We measured plasma obestatin and obestatin/ghrelin ratios.

Results: 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.

Conclusions: Obestatin and ghrelin release is differentially regulated by meal intake and the cholinergic system in lean individuals. This regulation is impaired in obesity.