Background And Aims: Cancer chemotherapy is commonly accompanied by mucositis, anorexia, weight loss, and anxiety independently from cancer-induced anorexia-cachexia, further aggravating clinical outcome. Ghrelin is a peptide hormone produced in gastric mucosa that reaches the brain to stimulate appetite. In plasma, ghrelin is protected from degradation by ghrelin-reactive immunoglobulins (Ig). To analyze possible involvement of ghrelin in the chemotherapy-induced anorexia and anxiety, gastric ghrelin expression, plasma levels of ghrelin, and ghrelin-reactive IgG were studied in rats treated with methotrexate (MTX).
Methods: Rats received MTX (2.5 mg/kg, subcutaneously) for three consecutive days and were killed 3 days later, at the peak of anorexia and weight loss. Control rats received phosphate-buffered saline. Preproghrelin mRNA expression in the stomach was analyzed by in situ hybridization. Plasma levels of ghrelin and ghrelin-reactive IgG were measured by immunoenzymatic assays and IgG affinity kinetics by surface plasmon resonance. Anxiety- and depression-like behaviors in MTX-treated anorectic and in control rats were evaluated in the elevated plus-maze and the forced-swim test, respectively.
Results: In MTX-treated anorectic rats, the number of preproghrelin mRNA-producing cells was found increased (by 51.3%, p < 0.001) as well were plasma concentrations of both ghrelin and des-acyl-ghrelin (by 70.4%, p < 0.05 and 98.3%, p < 0.01, respectively). In contrast, plasma levels of total IgG reactive with ghrelin and des-acyl-ghrelin were drastically decreased (by 87.2 and 88.4%, respectively, both p < 0.001), and affinity kinetics of these IgG were characterized by increased small and big Kd, respectively. MTX-treated rats displayed increased anxiety- but not depression-like behavior.
Conclusion: MTX-induced anorexia, weight loss, and anxiety are accompanied by increased ghrelin production and by a decrease of ghrelin-reactive IgG levels and affinity binding properties. Such changes of ghrelin-reactive IgG may underlie their decreased ghrelin-transporting capacities compromising ghrelin orexigenic and anxiolytic effects and contributing to chemotherapy-induced loss of appetite.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960292 | PMC |
http://dx.doi.org/10.3389/fnut.2016.00023 | DOI Listing |
Clin Nutr
August 2022
Department of Nutrition, Rouen University Hospital, CHU Rouen, France; Université de Rouen Normandie, Inserm UMR1073 « Nutrition, Inflammation and Microbiota-gut-brain Axis », Institute for Research and Innovation in Biomedicine, Rouen, France; Clinical Investigation Center CIC 1404 - Biological Resources Centre, Inserm, Rouen University Hospital, CHU Rouen, France. Electronic address:
Background & Aims: In the last decades, the role of microbiota-gut-brain axis has emerged in the regulation of eating behavior and in the pathophysiology of anorexia nervosa (AN) that remains poorly understood. Particularly, a gut-derived dysregulation of immune response has been proposed leading to immunoglobulins directed against appetite-regulating peptides. However, intestinal permeability in patients with anorexia nervosa has been poorly documented.
View Article and Find Full Text PDFExp Clin Endocrinol Diabetes
December 2022
Instituto de Investigaciones en Comportamiento Alimentario y Nutrición, Centro Universitario del Sur, Universidad de Guadalajara.
Dysfunctional eating patterns include alterations in experiencing and expressing hunger, appetite, and satiety, which may lead to eating disorders or obesity in the long term. Alterations in hormones such as ghrelin have been suggested to influence emotional eating in women with obesity. Ghrelin-reactive autoantibodies (autoAbs) are present both in healthy individuals and those with eating disorders and have been suggested to protect the hormone from degradation and preserve its functional activity.
View Article and Find Full Text PDFAppetite
January 2022
Instituto de Investigaciones en Comportamiento Alimentario y Nutrición, Centro Universitario del Sur, Universidad de Guadalajara, Av. Enrique Arreola Silva No. 883, 49000, Zapotlán el Grande, Jalisco, Mexico; Laboratorio de Biotecnología y Biomedicina para la Salud, Centro Universitario del Sur, Universidad de Guadalajara, Av. Enrique Arreola Silva No. 883, 49000, Zapotlán el Grande, Jalisco, Mexico. Electronic address:
Appetitive traits are important behavioural characteristics affecting eating and body composition. Ghrelin and leptin are two key hormones regulating appetite and metabolism. Recent studies have reported the presence of autoantibodies (autoAbs) directed to ghrelin and leptin in healthy individuals as well as affinity alterations in eating disorders such as anorexia nervosa and hyperphagic obesity.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2017
INSERM UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen Normandy, Rouen, France.
Part of circulating ghrelin is bound to immunoglobulins (Ig) protecting it from degradation and preserving its functional activity. This review summarizes the data on ghrelin- and desacyl-ghrelin-reactive IgG in conditions of altered appetite and energy balance. Plasma levels and affinity kinetics of such IgG were compared in patients with obesity and anorexia nervosa (AN) and in animal models of obesity including mice, high-fat diet-induced obese mice, and obese Zucker rats as well as in mice after chronic food restriction and activity-based anorexia and in rats with methotrexate-induced anorexia.
View Article and Find Full Text PDFNutrition
July 2018
Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Normandy, France.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!