Abstract

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 °C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 °C, 25 °C, or vehicle at 21 °C, 25 °C and 32 °C for a week. Animals housed at 32 °C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 °C, body temperature of leptin infused animals housed at 21 °C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa.

Highlights

  • The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats

  • The aims of this study are twofold: 1) to replicate the original study performed by Exner et al.[19], and to compare the efficacy of leptin and heightened Ta in SIH model in order to determine if housing temperature and not leptin plays a critical role in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa in humans

  • On the last day of the RF phase (Day 6), the activity of animals housed at 21 °C was eight (21VH) to ten times (21LEP) higher than the activity of warmed rats, and no significant differences were found between groups housed at 21 °C, except on Day 1 when running activity of leptin infused rats was significantly lower than in vehicle treated rats (p = 0.025)

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Summary

Introduction

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. The negative vicious cycle between diet and exercise is reproduced in two analogous animal models that mimic weight loss and hyperactivity, as well as many others signs in AN; the activity based anorexia (ABA) model[10], and the semi-starvation induced hyperactivity (SIH) model[11] Both models focus on the excessive activity of food-restricted rats but whilst ABA underlines the effect of running activity in food intake, that is, self-starvation[12], SIH focuses on the effects of food restriction on the increase of running activity. Previous research in rats exposed to ABA has shown that the supply of heat[22,23,24] prevented excessive running and weight loss In this sense, increased ambient temperature (Ta), both reversed excessive activity and improved food intake allowing bodyweight recovery, an effect replicated in male and female animals[25,26,27]

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