Physiological regulation of ghrelin by nutrient load in lean and obese subjects

Ghrelin is thought to be an important regulator of food intake. Intriguingly, it is produced primarily by cells in the oxyntic gland of the stomach. To understand its regulation in more detail, circulating ghrelin levels were studied in lean and obese subjects, and after different nutrient loads.

Fasting ghrelin levels were measured in 143 normal subjects (mean BMI 25.1±0.4kg/m², range 16–42). Seven healthy subjects (mean BMI 24.6±1.6kg/m²) were studied on three different days after ingestion of a standardized test meal (MEAL), 75g glucose (GLUC), or 0.7l water (H2O). Furthermore, seven obese subjects (mean BMI 43.9±4.5kg/m²) were studied after GLUC. For dynamic testing, blood samples were collected at 0', 30', 60', 90', and 120'. Ghrelin levels were measured by a commercial radioimmunoassay (Phoenix Pharmaceuticals).

Determination of ghrelin levels revealed a weak, but significant correlation with weight (r=0.45, p<0.0001) and BMI (r=0.36, p<0.0001), but not with age. In normal weight subjects, ghrelin continuously rose to a maximum of 114±5.6% of basal levels after ingestion of H2O. Ingestion of GLUC lead to an immediate drop in ghrelin levels to a minimum of 67±5.4%. In contrast, ingestion of MEAL was characterized by an increase in Ghrelin levels at 30' to 112±4.4%, followed by a drop to 87±5.7% of basal levels. In obese subjects, ingestion of GLUC was followed by a drop of ghrelin levels to 70±4.3% of basal levels.

Lower fasting ghrelin levels in obese subjects may indicate a negative feedback of overweight. However, the suppressive effect of oral glucose did not differ between lean and obese subjects. The difference in ghrelin suppression during GLUC and MEAL may be related to different resorption rates or diet composition. Gastric distension alone by water is not sufficient for suppression of ghrelin levels.