title: Eating behavior disorders in uremia: a question of balance in appetite regulation.
abstract: Eating and appetite disorders are frequent complications of the uremic syndrome which contribute to malnutrition in dialysis patients. The data suggest that uremic anorexia may occur with or without abdominal and visceral fat accumulation despite a lower food intake. This form of obesity (i.e., with low food intake and malnutrition) is more common in dialysis patients than obesity with high food intake. This article reviews the current knowledge regarding mechanisms responsible for appetite regulation in normal conditions and in uremic patients. Anorexia in dialysis patients has been historically considered as a sign of uremic toxicity due to "inadequate" dialysis as judged by uncertain means ("middle molecule" accumulation, Kt/V, "peak-concentration hypothesis," and others). We propose the tryptophan-serotonin hypothesis, based on a uremia-induced disorder in patients' amino acid profile--low concentrations of large neutral and branched-chain amino acids with high tryptophan levels. A high rate of tryptophan transport across the blood-brain barrier increases the synthesis of serotonin, a major appetite inhibitor. Inflammation may also play a role in the genesis of anorexia and malnutrition. For example, silent infection with Helicobacter pylori may be a source of cytokines with cachectic action; its eradication improves appetite and nutrition. The evaluation of appetite should take into account cultural and social aspects. Uremic patients showed a universal trend to carbohydrate preference and red meat refusal compared to healthy people. In contrast, white meat was less problematic. Uremic patients also have a remarkable attraction for citrics and strong flavors in general. Eating preferences or refusals have been related to the predominance of some appetite peptide modulators. High levels of cholecystokinin (CCK) (a powerful anorexigen) are associated with early satiety for carbohydrates and neuropeptide Y (NPY) (an orexigen) with repeated food intake. Obesity and elevated body mass index often falsely suggest a good nutritional status. In uremic patients (a hyperinsulinemia state), disorders in the regulation of fat distribution (insulin, leptin, insulin-like growth factor [IGF]-1, fatty acids, and disorders in receptors for insulin, lipoprotein lipase, mitochondrial uncoupling protein-2, and beta 3 adrenoreceptors) may cause abdominal fat accumulation without an increase in appetite. Finally, appetite regulation in uremia is highly complex. Disorders in adipose tissue, gastrointestinal and neuropeptides, retained or hyperproduced inflammatory end products, and central nervous system changes may all play a role. Uremic anorexia may be explained by a hypothalamic hyperserotoninergic state derived from a high concentration of tryptophan and low branched-chain amino acids.
authors.affiliation: Servicio de Nefrología, Hospitales Universitarios de la Princesa y la Paz, Madrid, Spain.
authors.forename: Abelardo
authors.initials: A
authors.lastname: Aguilera
authors.forename: Rosa
authors.initials: R
authors.lastname: Codoceo
authors.forename: María A
authors.initials: MA
authors.lastname: Bajo
authors.forename: Pedro
authors.initials: P
authors.lastname: Iglesias
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Diéz
authors.forename: Guillermina
authors.initials: G
authors.lastname: Barril
authors.forename: Secundino
authors.initials: S
authors.lastname: Cigarrán
authors.forename: Vicente
authors.initials: V
authors.lastname: Alvarez
authors.forename: Olga
authors.initials: O
authors.lastname: Celadilla
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Perpén
authors.forename: Agustín
authors.initials: A
authors.lastname: Montero
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
mesh_terms: D001066:Appetite / Q000502:physiology*; D005247:Feeding Behavior; D001068:Feeding and Eating Disorders / Q000209:etiology* / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D044342:Malnutrition / Q000209:etiology; D009765:Obesity / Q000209:etiology; D006435:Renal Dialysis; D014511:Uremia / Q000150:complications* / Q000503:physiopathology* / Q000523:psychology