Obestatin has recently been identified as a peptide derived from pre-proghrelin that opposes ghrelin effects on appetite and body weight in rodents. We studied the effect of food intake on both these hormones in obese and lean subjects and recorded in parallel the subjective sensations of satiety and hunger. Eight obese (two males and six females, BMI=3152 kg/m2) and eight age- and sex-matched lean subjects (BMI=1923 kg/m2) were randomized to 1) take a standard breakfast and 2) time control studies after an overnight fast in a prospective cross-over study design. Obestatin and ghrelin plasma concentrations were quantified by radioimmunoassays, satiety and hunger by visual analogue scales.
Basal circulating obestatin was significantly decreased in obese as compared to lean humans and stable in both study groups during an observation period of 90 minutes. Thirty minutes after food intake, obestatin levels were markly reduced in obese subjects, but increased in lean controls. There was no correlation between ghrelin and obestatin postprandial plasma concentrations. Subjective ratings of satiety and hunger were significantly related to obestatin plasma concentrations only in lean subjects.
We conclude that obestatin concentrations are much lower in obese subjects and inversely regulated by food intake, as compared to lean subjects. Both fasting and postprandial suppression of the anorexigenic obestatin might be of relevance in the pathophysiology of the positive energy balance associated with obesity.