Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa?

Abstract

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.

Expanded insights into the neural component of the activity-based anorexia animal model — morphological changes in the enteric nervous system and altered pain perception

“…Some studies have shown that excessive exercise causes an increase in ALT levels [42,43], while other scientific reports suggest that regular mild physical activity lowers the ALT level [44,45]. In our study, the statistically significant lower level of ALT in the ABA group could have been caused by additional physical exercise, however, it is not consistent with our previous research on the animal model, which showed that the Expanded insights into the neural component of the activity-based anorexia animal model... liver enzymes were negatively affected by increased physical activity [30]. The ambiguous correlation between physical exercise and ALT levels could be the reason behind the different results in our studies.…”

“…There are a few proposed mechanisms including excessive exercise, depletion of liver glycogen, ineffective gluconeogenesis and issues with glucagon secretion [54]. In our experimental group, the glucose level was significantly lower than in the control group, and severe hypoglycemia was also observed in ABA rats -this is consistent with our previous study on the ABA model [30]. It is well established that hypoglycemia in ABA rodents is caused by food restriction, whereas in exercised controls the glucose level is not significantly altered [55][56][57].…”

“…Some studies also confirmed elevated levels of LDL and HDL among these individuals. The biological mechanism behind these changes is very complex and may be due to accelerated cholesterol metabolism, reduced catabolism and low concentrations of T3 [30,49]. In our study, ABA rats had significantly reduced levels of all four parameters of the lipid profile (total cholesterol, HDL, LDL, TG) compared to the control group.…”

“…In our previous study on the ABA model we confirmed that both physical activity and food restriction significantly lower the level of triglycerides. Regarding total cholesterol, we observed that exercise alone significantly decreases its level, while restricted feeding alone is related to a non-significant decrease [30]. However, the impact of food restriction on lowering the total cholesterol level in rats has been confirmed in the literature [58].…”

“…Thus, this study aimed to conduct a preliminary assessment of the ENS, which, due to its complexity, is gaining considerable interest in anorectic patients together with an analysis of pain threshold, an unresolved issue in AN. An activity-based rat model of anorexia (ABA), which is a reliable AN animal model [30,31], was applied in our study.…”