Ghrelin, Glucagon-like Peptide 1, and Peptide YY
Like levels of cholecystokinin, levels of ghrelin, glucagon-like peptide 1, and peptide YY change in relation to acute changes in food intake. Ghrelin, which is released from the stomach, exhibits diurnal variation, with the highest levels observed in the morning when the body is in a fasting state. Ghrelin levels decrease dramatically with food intake and then rise slowly during the periods leading up to subsequent meals during the day. Ghrelin triggers food intake in animals and humans and is linked to subjective reports of hunger in humans. Based on its time course and its effects in experimental studies in animals, ghrelin is considered a hunger hormone that stimulates eating.
Glucagon-like peptide 1 shows a pattern of release and function very similar to that of cholecystokinin and likewise triggers stimulation of the vagus nerve to stimulate satiety centers of the brain. Levels of cholecystokinin and glucagon-like peptide 1 peak within 30 minutes after the end of a meal. Cholecystokinin and glucagon-like peptide 1 are considered short-term satiation peptides that help signal when an eating episode should stop.
Peptide YY is released from lower in the intestinal tract than cholecystokinin and glucagon-like peptide 1, and its levels rise more slowly than levels of those neuropeptides. Peptide YY levels peak approximately 50-90 minutes after the end of a meal and do not subside until approximately two hours after the meal. Peptide YY is seen as a satiety peptide that delays the onset of the next eating episode (e.g., the onset of lunch after breakfast or the onset of dinner after lunch) rather than as a satiation peptide that terminates a current eating episode.
Studies of AN patients suggest that they have higher fasting concentrations of ghrelin than controls (A. C. Prince et al., 2009; Tong & D’Alessio, 2011), which may be a consequence of their dietary restriction. In contrast, findings for fasting ghrelin concentrations in BN have been mixed (A. C. Prince et al., 2009). Patients with BN may experience a less robust decrease in ghrelin after food intake than control participants (Kojima et al., 2005; Monteleone et al., 2005). For AN, findings on ghrelin response to food intake have been inconsistent (A. C. Prince et al., 2009; Tong & D’Alessio, 2011). Studies of BED have also produced mixed results: One study found no differences in fasting ghrelin concentrations or in ghrelin response to food intake between control and BED participants (Munsch, Biedert, Meyer, Herpertz, & Beglinger, 2009), while another suggested that BED patients have lower fasting concentrations of ghrelin and a less robust decrease in ghrelin after food intake (Geliebter, Hashim, & Gluck, 2008). The disrupted circadian rhythm in night eating syndrome is associated with disruptions in circadian release of ghrelin (K. C. Allison et al., 2005; Rosenhagen, Uhr, Schussler, & Steiger, 2005; Goel et al., 2009; Birketvedt, Geliebter, Kristiansen, Firgenschau, Goll, & Florholmen, 2012).
Research indicates lower levels of glucagon-like peptide 1 in women with BN than in controls (Naessen, Carlstrom, Holst, Hellstrom, & Hirschberg, 2011; Dossat, Bodell, Williams, Eckel, & Keel, 2015). Patients with BN have also been found to have significantly lower glucagon-like peptide 1 levels than do patients with purging disorder (Dossat et al., 2015). Patients with AN had higher levels of glucagon-like peptide 1 than controls in one study (Germain et al., 2007), while another found that they had lower-than-control levels of this neuropeptide (Tomasik, Sztefko, & Starzyk, 2004). No differences have been reported in glucagon-like peptide 1 levels between controls and women with BED (Geliebter et al., 2008) or purging disorder (Dossat et al., 2015).
For peptide YY, two studies have supported blunted responses to food intake in BN compared with controls (Kojima et al., 2005; Monteleone et al., 2005), while another observed no difference in peptide YY response (Devlin et al., 2012). A significantly decreased peptide YY response to food intake in AN patients was found in one study (Stock et al., 2005), a significantly increased response in another (Nakahara et al., 2007), and no significant difference in a third (Otto et al., 2007). For BED, one study found no differences from controls in postmeal peptide YY release (Geliebter et al., 2008), while another suggested an elevated peptide YY response (Munsch et al., 2009).
Taken together, results suggest that AN is consistently associated with lower leptin, higher neuropeptide Y, and higher ghrelin concentrations than seen in controls, all of which should promote increased hunger and food intake. However, patients with AN often deny hunger and they restrict their food intake. While these differences may not explain selfstarvation in AN, they might contribute to risk for binge eating in the illness (A. C. Prince et al., 2009). Mixed results have emerged for other neuropeptides in AN.
For BN, the picture is clearer. Despite maintaining a normal weight, individuals with BN have lower leptin concentrations, higher neuropeptide Y concentrations, and less robust changes in the neuropeptides that alleviate hunger (ghrelin) and produce short-term satiation (cholecystokinin and glucagon-like peptide 1) and long-term satiety (peptide YY) compared to controls. Although it is unclear whether these differences were present before the onset of BN, all would contribute to maintenance of binge eating in the disorder.
Few consistent results concerning neuropeptides have emerged to explain the unique patterns of disordered eating behavior in BED, night eating syndrome, and purging disorder.
For BED, one challenge is distinguishing alterations in neuropeptide levels and responses that may be part of the eating disorder versus those that are linked to obesity, making it is important to employ a weight-matched control group. However, doing so creates a particularly high threshold for identifying alterations uniquely associated with binge eating, given that much of the research on neuropeptides has indicated considerable overlap between factors that regulate eating behavior and weight.