Unexpected Association of Desacyl-Ghrelin with Physical Activity and Chronic Food Restriction: A Translational Study on Anorexia Nervosa

Abstract

Anorexia nervosa (AN) is a severe metabopsychiatric disorder characterised by caloric intake restriction and often excessive physical exercise. Our aim is to assess in female AN patients and in a rodent model, the co-evolution of physical activity and potential dysregulation of acyl—(AG) and desacyl—(DAG) ghrelin plasma concentrations during denutrition and weight recovery. AN inpatients were evaluated at inclusion (T0, n = 29), half—(T1) and total (T2) weight recovery, and one month after discharge (T3, n = 13). C57/Bl6 mice with access to a running wheel, were fed ad libitum or submitted to short—(15 days) or long—(50 days) term quantitative food restriction, followed by refeeding (20 days). In AN patients, AG and DAG rapidly decreased during weight recovery (T0 to T2), AG increased significantly one-month post discharge (T3), but only DAG plasma concentrations at T3 correlated negatively with BMI and positively with physical activity. In mice, AG and DAG both increased during short- and long-term food restriction. After 20 days of ad libitum feeding, DAG was associated to persistence of exercise alteration. The positive association of DAG with physical activity during caloric restriction and after weight recovery questions its role in the adaptation mechanisms to energy deprivation that need to be considered in recovery process in AN.

A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa

“…The two different approaches (change from baseline to follow-up and follow-up to HCs) were repeated for a longitudinal analysis of acyl ghrelin values. Longitudinal analysis of acyl ghrelin in five studies [ 67 , 69 , 74 , 78 , 79 ] provided data at seven follow-up time points, including a total of 77 AN patients (providing 135 data points). Four studies included patients in an inpatient setting, including a nutritional rehabilitation program (n = 2) and nutritional program combined with cognitive behavioural therapy (n = 2) and one study did not provide treatment.…”

“…However, results of the current meta-analysis also showed significant increases in acyl ghrelin during the acute state, possibly opposing this theory. Moreover, one study showed desacyl ghrelin to be particularly associated with BMI and physical activity [ 79 ].…”

Exploring the Mechanisms of Recovery in Anorexia Nervosa through a Translational Approach: From Original Ecological Measurements in Human to Brain Tissue Analyses in Mice

“…In patients with AN, plasma variations of AG and DAG during the weight restoration period might be considered as reliable biomarkers of a successful recovery [ 31 ]. Indeed, we recently showed that DAG plasma concentration after weight restoration is associated with instable recovery and an increase in physical activity after discharge [ 32 ]. However, an accurate measurement of physical activity in AN remains difficult and data are still lacking, limiting translational benefits from preclinical models such as the activity-based rodent model of AN [ 33 ].…”

Advances in Eating Disorders

“…To address this important health issue, the current Special Issue collected 21 articles examining the most recent and relevant scientific findings regarding advances in ED. The published articles comprised three reviews and 18 research articles focusing on different aspects, such as genetic [ 7 ] and epigenetic factors [ 8 ], biomarkers [ 9 ], comorbidity [ 10 , 11 , 12 , 13 , 14 ], clinical phenotypes [ 15 , 16 ], neurocognition [ 12 , 17 , 18 , 19 , 20 , 21 ], treatment predictors [ 22 ], and treatment models and therapeutic targets [ 19 , 23 , 24 , 25 , 26 , 27 ]. Altogether, these studies may provide increased knowledge about the pathogenesis, the risk factors, the maintenance factors, and the most appropriate treatments tools for ED.…”

“…The identification of biomarkers was also a relevant topic addressed in this issue. Duriez et al [ 9 ], in a translational study, aimed to determine whether some biomarkers, such as acyl-ghrelin (AG) and desacyl-ghrelin (DAG) plasma concentrations, reflect the level of physical activity during food restriction and after renutrition. Authors found that, in experimental models of mice, AG and DAG both increased during food restriction.…”