Emilio Gutierrez

Activity-based anorexia: ambient temperature has been a neglected factor.

Activity-based anorexia refers to the self-starvation of rats exposed to experimental conditions that combine restricted access to food with access to an activity wheel. This paper compares previous studies of this phenomenon in relation to the ambient temperatures (AT) that were employed. On this basis, and from some more direct evidence, we argue that AT is an important, but neglected, factor in activity-based anorexia research. More attention to AT is needed in future research, since its neglect threatens the validity of conclusions drawn from those studies. Furthermore, direct examination of the effect of AT on activity-based anorexia will allow a better understanding of the mechanisms underlying this phenomenon and the possible clinical implications for the treatment of human anorexia nervosa.

A rat in the labyrinth of anorexia nervosa: contributions of the activity-based anorexia rodent model to the understanding of anorexia nervosa.

Activity-based anorexia (ABA) is an analogous animal model of anorexia nervosa where food-restricted rats develop excessive running activity when given free access to a running wheel; their body weight sharply decreases, and finally self-starvation and death ensue unless animals are removed from the experimental conditions. The parallel of this animal model with major signs in the human disorder has been the focus of much attention from researchers and clinicians as a platform for translational research. The paper reviews the historical antecedents of ABA, research characterizing its occurrence, and its main limitations and strengths as a model of AN. As a symptomatic model of AN, the ABA model can provide clinicians with innovative and alternative routes for improving the treatment of AN.

Hyperactivity in Anorexia Nervosa: Warming Up Not Just Burning-Off Calories

Excessive physical activity is a common feature in Anorexia Nervosa (AN) that interferes with the recovery process. Animal models have demonstrated that ambient temperature modulates physical activity in semi-starved animals. The aim of the present study was to assess the effect of ambient temperature on physical activity in AN patients in the acute phase of the illness. Thirty-seven patients with AN wore an accelerometer to measure physical activity within the first week of contacting a specialized eating disorder center. Standardized measures of anxiety, depression and eating disorder psychopathology were assessed. Corresponding daily values for ambient temperature were obtained from local meteorological stations. Ambient temperature was negatively correlated with physical activity (p = −.405) and was the only variable that accounted for a significant portion of the variance in physical activity (p = .034). Consistent with recent research with an analogous animal model of the disorder, our findings suggest that ambient temperature is a critical factor contributing to the expression of excessive physical activity levels in AN. Keeping patients warm may prove to be a beneficial treatment option for this symptom.

Heat in the treatment of patients with anorexia nervosa

The paper presents the results of heat treatment in three cases of anorexia nervosa (AN), in which marked overactivity and/or strenuous exercising were prominent clinical features. Heat was supplied in three ways: continuous exposure to a warm environment, wearing a thermal waistcoat, and sauna baths in an infrared cabin. The outcomes went far beyond what had been expected, as the disappearance of hyperactivity was followed by progressive recovery.

High ambient temperature reduces rate of body-weight loss produced by wheel running

This study examined the effect of ambient temperature (AT) on the relationship between activity and weight loss. Compared with a neutral AT of 21°C, high ATs of 27–29°C produced a slower rate of weight loss in rats given 1.5-hr food access and 22.5-hr running-wheel access in a standard activity-based anorexia (ABA) procedure (Experiments 1 and 2). The high AT did not affect food intake or wheel running in Experiment 1, but did reduce running in Experiment 2. Switching from neutral to high AT had only a transient effect on weight loss when wheel access was maintained (Experiment 2) but resulted in less weight loss when wheel access was prevented (Experiment 3). Giving rats only 3 hr of wheel access each day at a neutral AT also produced substantial weight loss, but less if for the rest of each day they were maintained at a high AT (Experiment 4).

Heat reversal of activity-based anorexia: Implications for the treatment of anorexia nervosa

OBJECTIVE Activity-based anorexia (ABA) provides an animal model of anorexia nervosa (AN). In this model, rats given restricted access to food but unrestricted access to activity wheels, run excessively while reducing food intake, lose a sizeable percentage of body weight, become hypothermic, and can fail to recover unless removed from these conditions. METHOD Once rats had lost 20% of body weight under standard ABA conditions, they were assigned to one of two ambient temperature (AT) conditions. RESULTS Increased AT reduced running rates and led to weight gain in active rats. The effect of increasing AT on food intake was dependent on whether the rats were sedentary or active. Although warming reduced food intake in the sedentary rats their body weight remained stable, whereas in active rats increased AT did not reduce food intake and weight gain gradually rose. CONCLUSION From a translational perspective, these findings offer a fresh perspective to the disorder, and underscore the need for further studies to assess the effects of heat treatment in patients as an innovative adjunctive treatment for anorexia nervosa.

Heat makes a difference in activity‐based anorexia: A translational approach to treatment development in anorexia nervosa

OBJECTIVE To test the effect of raising ambient temperature (AT) on activity-based anorexia (ABA) and to extend to female rats previous findings reported in male animals. METHOD Two studies are reported in which female rats were submitted to food restriction and free access to an activity wheel either separately or in combination under changing (21-32 °C) or constant AT (21 °C). RESULTS Warming ABA animals reversed running activity, preserved food-intake, and enabled female rats to recover from acute weight loss. Moreover, sedentary food-restricted warmed rats maintained a body weight equivalent to the levels of animals housed at standard AT in spite of 20% reduced food-intake. DISCUSSION The replication on female rats corroborates the effect previously reported for males, which is indicative of the robust effect of AT in recovering rats from ABA. The findings reported here represent strong preclinical evidence in favor of heat supply as a useful adjunctive component for the treatment of anorexia nervosa (AN).

High ambient temperature reverses hypothalamic MC4 receptor overexpression in an animal model of anorexia nervosa.

The potential involvement of the melanocortin system in the beneficial effects of heat application in rats submitted to activity-based anorexia (ABA), an analogous model of anorexia nervosa (AN), was studied. Once ABA rats had lost 20% of body weight, half of the animals were exposed to a high ambient temperature (HAT) of 32 degrees C, whereas the rest were maintained at 21 degrees C. Control sedentary rats yoked to ABA animals received the same treatment. ABA rats (21 degrees C) showed increased Melanocortin 4 (MC4) receptor and Agouti gene Related Peptide (AgRP) expression, and decreased pro-opiomelanocortin (POMC) mRNA levels (Real Time PCR), with respect to controls. Heat application increased weight gain and food intake, and reduced running rate in ABA rats, when compared with ABA rats at 21 degrees C. However, no changes in body weight and food intake were observed in sedentary rats exposed to heat. Moreover, heat application reduced MC4 receptor, AgRP and POMC expression in ABA rats, but no changes were observed in control rats. These results indicate that hypothalamic MC4 receptor overexpression could occur on the basis of the characteristic hyperactivity, weight loss, and self-starvation of ABA rats, and suggest the involvement of hypothalamic melanocortin neural circuits in behavioural changes shown by AN patients. Changes in AgRP and POMC expression could represent an adaptative response to equilibrate energy balance. Moreover, the fact that HAT reversed hypothalamic MC4 receptor overexpression in ABA rats indicates the involvement of brain melanocortin system in the reported beneficial effects of heat application in AN. A combination of MC4 receptor antagonists and heat application could improve the clinical management of AN.

Exploring the association between anorexia nervosa and geographical latitude

Objective: This paper explores the relationship between anorexia nervosa (AN) and climate by mapping the distribution of references of AN in the literature at different latitudes. Method: The distributions of the bibliographic references of two medical disorders -psoriasis and cataracts-, and four mental disorders -AN, anxiety disorders, seasonal affective disorders, and schizophrenia- were mapped according to the institutional affiliation of their first author. Results: The distribution of references to AN was quite similar to the mental and medical disorders associated to high latitudes, although references to AN were more frequent in the range of 40°–55° in the Northern Hemisphere. Discussion: The psychosocial and sociocultural features of ‘cultures’ do not exhaust the factors defining the environment in which we live. Our findings indicate that climatic parameters, such as latitude may be a relevant factor in the occurrence of AN.

Gender dimorphic effects of voluntary running in laboratory rats depends on maturational status

This study examined the effect of 24 hr per day wheel access on running, body weight, and food intake for 30- or 50-day-old male and female rats under ad lib feeding conditions. Food intake and body weight were also monitored in a control group housed without access to running wheels. A dimorphic effect was observed after wheel introduction in 50-day-old but not 30-day-old rats: A temporary decline in food intake and a lasting decrease in body weight occurred for active male rats in comparison to their sedentary controls, and wheel access facilitated food intake and preserved body weight gain in female rats in comparison to their sedentary counterparts. Hyperphagia in adult females is interpreted in terms of the evolutionary acquired advantage linked to their reproductive function.