The Use of Animal Models to Decipher Physiological and Neurobiological Alterations of Anorexia Nervosa Patients

Abstract

Extensive studies were performed to decipher the mechanisms regulating feeding due to the worldwide obesity pandemy and its complications. The data obtained might be adapted to another disorder related to alteration of food intake, the restrictive anorexia nervosa. This multifactorial disease with a complex and unknown etiology is considered as an awful eating disorder since the chronic refusal to eat leads to severe, and sometimes, irreversible complications for the whole organism, until death. There is an urgent need to better understand the different aspects of the disease to develop novel approaches complementary to the usual psychological therapies. For this purpose, the use of pertinent animal models becomes a necessity. We present here the various rodent models described in the literature that might be used to dissect central and peripheral mechanisms involved in the adaptation to deficient energy supplies and/or the maintenance of physiological alterations on the long term. Data obtained from the spontaneous or engineered genetic models permit to better apprehend the implication of one signaling system (hormone, neuropeptide, neurotransmitter) in the development of several symptoms observed in anorexia nervosa. As example, mutations in the ghrelin, serotonin, dopamine pathways lead to alterations that mimic the phenotype, but compensatory mechanisms often occur rendering necessary the use of more selective gene strategies. Until now, environmental animal models based on one or several inducing factors like diet restriction, stress, or physical activity mimicked more extensively central and peripheral alterations decribed in anorexia nervosa. They bring significant data on feeding behavior, energy expenditure, and central circuit alterations. Animal models are described and criticized on the basis of the criteria of validity for anorexia nervosa.

Intestinal microbiota and Anorexia Nervosa

“…Much effort is now required to identify how remodeling of the gut microbiota may impact the onset or the course of anorexia. Animal models of AN may constitute interesting tools to tackle these questions [74]. Transplantation of microbiota from anorectic patients to mice and measurement of intestinal physiology alterations, metabolic and behavioral changes specific to the composition of the grafted microbiota would also greatly help to identify enteric micro-organisms that have a detrimental or beneficial impact in AN.…”

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

“…Several other anorexia models have been developed encompassing genetically engineered mouse models that share similarities with changes observed in AN; however, none of these reflect the multiple hormonal changes observed in AN (Méquinion et al, 2015). Lastly, other models use access to low caloric food or expose rats to various kinds of stressors (Méquinion et al, 2015).…”

“…Lastly, other models use access to low caloric food or expose rats to various kinds of stressors (Méquinion et al, 2015). However, it is important to note that so far activity-based anorexia is considered the best animal model (Gutierrez, 2013) as it recapitulates two main features, physical activity and reduced food intake, of human AN.…”

The Ghrelin-AgRP Neuron Nexus in Anorexia Nervosa: Implications for Metabolic and Behavioral Adaptations

“…Rodents, like humans, adopt similar strategies to cope with acute or chronic energy deficit in order to maintain vital signs in homeostatic range and organ functions (102,103). At the level of AgRP neurons, food deprivation leads to changes in gene expression in pathways involved in hormone signaling, including leptin, insulin and ghrelin that leads to modulation of AgRP, NPY and GABA expression (104).…”