Reprinted from Eating Disorders Review
January/February 2004 Volume 15, Number 1
©2004 Gürze Books
The recent discovery of ghrelin, an amino acid peptide, has added to our understanding of the body’s control of food intake and energy balance. Ghrelin, which is secreted mainly by the stomach and duodenum, stimulates hunger and promotes food ingestion. In contrast, leptin, another endogenous protein, increases satiety and reduces food consumption.
Results of two recent studies have shown that ghrelin can be a helpful marker of nutritional status among patients with obesity and anorexia nervosa, and that bulimia nervosa causes a profound dysregulation of this peptide.
A marker among obese and anorexic patients
In the first study, at the Hospital Infantil Universitario Nino Jesus, in Madrid, Dr. Leandro Soriano-Guillen and colleagues studied the effects of dietary intervention among 16 prepubertal children who were obese, 16 anorexic adolescents, and 41 healthy controls (21 were prepubertal and 20 were in Tanner growth stage 5). The researchers analyzed plasma ghrelin levels and their correlation with plasma levels of leptin, insulin, and insulin-like growth-factor-binding proteins 1 and 2 (J Pediatr 2004;144:36).
At diagnosis, ghrelin levels were significantly decreased in obese children (52% of control levels) and significantly increased in adolescents with anorexia nervosa (64% of control levels). After dietary intervention, ghrelin increased in obese patients without reaching control levels even after a 50% reduction in body mass index (BMI). In adolescents with AN, ghrelin levels normalized after a 25% increase in BMI. Ghrelin levels correlated negatively with the BMI and positively with IGFBP-1 levels in controls but not in obese patients or in patients with AN.
Ghrelin’s effect is blunted among patients with BN
In the second study, Dr. Palmiero Monteleone and colleagues at the University of Naples, Italy, compared the response of ghrelin and leptin to a meal in two groups—untreated women with bulimia nervosa and normal controls. Nine symptomatic drug-free bulimic women and 12 age-matched healthy women ingested a meal of 1,207 kcal (60% carbohydrate, 23% fat, 17% protein) at 12 noon.
The bulimic women were all of the purging subtype, with binge episodes always followed by self-induced vomiting; none abused laxatives or exercised excessively. Three had a past history of anorexia nervosa, 2 had concomitant generalized anxiety disorder, and 3 had an Axis II diagnosis of borderline personality disorder. Control women were within 15% of their ideal body weight, had normal diets and no family history of mental disorders.
Blood samples were collected before, and then 45, 60, 90, 120, and 180 minutes after the meal. Plasma levels of ghrelin, leptin, insulin, and glucose were measured. Glucose and insulin levels were of interest because these substances have been claimed to modulate ghrelin secretion in response to food intake.
There were no significant differences between the bulimic patients and the control women in age, body weight, BMI, body fat mass and body lean mass. In addition, pre-meal levels of ghrelin, leptin, insulin, and glucose did not differ between the groups.
The ghrelin response to food intake was significantly blunted in the bulimic patients, and postprandial profiles of circulating leptin, insulin, and glucose were not significantly different between patients and controls.
The authors reported that, just as with other studies, food consumption dramatically decreased plasma ghrelin concentrations in healthy subjects. In untreated symptomatic bulimic women, the suppression of circulating ghrelin by food intake was significantly blunted.
The authors note that study results suggest that ghrelin is a starvation-related hormone that functions as an indicator of short-term changes in energy balance Therefore, its suppression after food ingestion may represent a peripheral signal involved in the regulation of a meal size by reducing hunger and/or increasing satiety. Therefore, finding a blunted response of circulating ghrelin to food in symptomatic bulimics would support impaired suppression of the drive to eat following a meal that could be responsible for an increased food consumption and binge eating among this group of patients. Laboratory studies of humans suggest that bulimic patients have diminished satiety responses to meals (Walsh et al, 1989) that, on the basis of the results of the study, could be mediated at least in part by impaired suppression of ghrelin secretion.
Precise mechanisms are still a mystery
The mechanisms underlying the altered ghrelin response to food in bulimia nervosa are not known. But, could altered glucose or insulin responses to a meal cause a blunted ghrelin response in bulimic patients? The authors didn’t observe any difference in postprandial plasma glucose and insulin levels between bulimic patients and controls.
Another suggested theory is that the disordered eating particularly chronic fasting-gorging behavior of bulimic women, impairs the ghrelin sensitivity to acute changes in energy intake. Despite the large amount of calories ingested during binge episodes, bulimics regurgitate a relatively large amount of calories through vomiting and may use prolonged starvation to reduce their daily caloric intake. Since insulin and glucose are believed to be involved in the postprandial mechanisms by suppressing ghrelin production, repeated abrupt decrements following chronic purging episodes may damage the sensitivity of ghrelin-producing cells to these physiological regulators. Then, even if bulimics have normal postprandial levels of circulating insulin and glucose, their sensitivity to food-induced ghrelin suppression could be impaired. The absence of changes in leptin levels immediately after food consumption lends support to the idea that leptin is not involved in regulating meal size and postprandial satiety.
The study shows for the first time that the ghrelin response to food consumption is significantly blunted in symptomatic bulimics, whereas the short-term leptin response is preserved. These findings support the authors’ theory that in BN a profound dysregulation of some peripheral regulatory mechanisms is involved in both short-term and long-term regulation of feeding behavior and energy balance.