Ghrelin, Peptide YY, Glucose-Dependent Insulinotropic Polypeptide, and Hunger Responses to a Mixed Meal in Anorexic, Obese, and Control Female Adolescents

Abstract

To determine whether peptide YY (PYY), ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and satiety responses to food intake are impaired in anorexia or obesity, we studied 30 female adolescents with anorexia nervosa [body mass index (BMI) 16.3 kg/m2], obesity (BMI 34.3 kg/m2), or normal weight (BMI 20.2 kg/m2). PYY, ghrelin, GIP, insulin, and glucose concentrations and four markers of satiety were measured for 240 min after a mixed meal. The area under the curve for glucose was similar in obese (OB) and normal-weight control (C) subjects but was 15% lower in anorexic (AN) subjects. The area under the curve for insulin was 47% lower in AN and 87% higher in OB subjects, compared with C subjects. After the meal, PYY increased significantly in C (+41%, P < 0.05) but not in AN or OB adolescents. Ghrelin concentrations were highest in AN subjects and lowest in the OB group, compared with C subjects and fell significantly by 25% in all three groups. GIP concentrations were lower in AN subjects throughout the test and increased in all three groups after the mixed meal. AN adolescents reported being less hungry than OB and C adolescents. There was a negative correlation between fasting ghrelin (but not PYY or GIP) and BMI and insulin (r2= 0.33) and a positive correlation between the decrease in hunger 15 min after the meal and PYY concentrations at 15 min (r2= 0.20). In conclusion, the blunted PYY response to a meal in OB adolescents suggests that PYY plays a role in the pathophysiology of obesity. Ghrelin is unlikely to play a causal role in anorexia nervosa or obesity. The lower GIP observed in AN subjects despite a similar caloric intake may appropriately prevent an excessive insulin response in these patients.

The role of peptide YY in regulating glucose homeostasis

“…This study showed that the PYY was comparable between lean and obese people, despite the fact that the obese people were more insulin resistant and produced significantly more insulin in response to glucose [27]. Another study found no correlation between circulating PYY or insulin levels in normal, obese and anorexic subjects [44].…”

“…Although these studies suggest that PYY1-36 or PYY3-36 do not have a role in glucose homeostasis, it is important to highlight that PYY levels were measured in obese people that already have high fasting insulin [5], in diabetic subjects that were already insulin resistant [17] or in anorexic subjects who had an eating disorder and were likely to have an altered PYY response in addition to having decreased baseline insulin levels [44]. Indeed it is feasible that these obese, diabetic and anorexic subjects may have decreased sensitivity to PYY1-36 and PYY3-36, which normally function to influence glucose-stimulated insulin secretion or insulin sensitivity, respectively.…”

Effects of a high-fat meal on postprandial incretin responses, appetite scores and ad libitum energy intake in women with obesity

“…Other studies have founded that postprandial GIP response was inversely related to the subsequent feeling of satiety (5,12,13). On the other hand, positive (14) or neutral (9,10,15) correlation between postprandial GIP and satiety were also observed.…”

Obesity vaccines

“…36 In most patients there is a negative correlation between fasting ghrelin levels and body mass index, reflecting the presence of an adequate physiological response, with low or high ghrelin levels in the context of positive or negative energy balance, respectively. Consequently, fasting ghrelin levels are usually low in obese subjects compared with controls, 37 although levels rise after diet induced weight loss. 35,38 In contrast, patients with nervous anorexia have high fasting ghrelin levels.…”