Agouti-related protein (AGRP) is the competitive antagonist of alpha-melanocyte stimulating hormone (α-MSH) located at melanocortin receptors 3 and 4 (MC3R and MC4R), and also acts as an MC4R inverse agonist. Hypothalamic AGRP controls food intake and body weight in rodents. It has also been found in human plasma. To study the possibility of disturbances in melanocortin receptor-related peptides in eating disorders, plasma AGRP, α-MSH, and leptin levels were measured in 18 female patients with anorexia nervosa (AN) (age, 23.5±7.1 yr; body mass index (BMI) 14.5±1.8 kg/m2) and 17 age-matched female controls (age, 25.8±3.9 yr; BMI 20.2±1.6 kg/m2). Blood samples were collected after overnight fasting, and plasma peptides levels were measured using ELISA. Plasma AGRP levels increased significantly in AN patients when compared with controls (P<0.01) while plasma α-MSH levels were not significantly different. Plasma leptin levels decreased significantly in AN patients when compared with controls (P<0.001). In addition, plasma AGRP levels were negatively correlated with leptin (r=−0.41, P<0.01) and BMI (r=−0.40, P<0.05) in all subjects. In conclusion, plasma AGRP elevation may be related to energy homeostasis disturbance in AN, and in addition to leptin, peripheral AGRP levels could be used as a nutritional marker in AN patients.
Anorexia nervosa (AN) is an eating disorder characterized by decreased caloric intake, low weight, and reduced body fat. AN is diagnosed by weight loss and a refusal to maintain a minimal normal body weight, an intense fear of gaining weight or becoming fat, a self-evaluation unduly influenced by body shape and weight, and amenorrhea. Though the pathophysiology of AN is still unclear, an imbalance in neuropeptides controlling food intake and body weight has been found to be related to this disorder (Bailer and Kaye, 2003).
The hypothalamic agouti-related protein (AGRP) controls food intake and body weight in rodents (Schwartz et al., 2000). AGRP is the competitive antagonist of alpha-melanocyte stimulating hormone (α-MSH) located at melanocortin receptors 3 and 4 (MC3R and MC4R) ( Schwartz et al., 2000), and also acts as an MC4R inverse agonist ( Nijenhuis et al., 2001). AGRP mRNA has been found in the brain, adrenal gland, lung, and testis of humans ( Ollmann et al., 1997; Li et al., 2000). It has also been found in human plasma. The function of systemically circulating AGRP, however, remains unknown.
Previous studies have shown that plasma AGRP and α-MSH are associated with obesity in human populations ( Katsuki et al., 2001; Hoggard et al., 2004). Peripheral AGRP levels in blood increase with fasting ( Shen et al., 2002; Gavrila et al., 2005). Also, an association between AN and AGRP gene polymorphism (G760A) has been reported ( Vink et al., 2001), suggesting that AGRP may be related to the pathogenesis of AN.
In this study, the plasma levels of AGRP, α-MSH, and leptin in AN and healthy age-matched women were measured in order to determine the possibility of disturbance in these three peptides in AN. This is the first study to examine plasma AGRP and α-MSH in AN patients in relation to leptin.
