Temperature but not leptin prevents semi-starvation induced hyperactivity in rats: implications for anorexia nervosa treatment

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 nervosaResearch leading to these results has received funding from the research budget from the Unidade Venres Clinicos (E.G., A.F.) and the Xunta de Galicia (ML: 2015-CP079 and 2016-PG068); Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Program of EU (ML: RTI2018-101840-B-I00 and BFU2015-70454-REDT/Adipoplast) and Atresmedia Corporación (ML); MC, AGI, (CIBERobn), Xunta de Galicia and Instituto de Salud Carlos III (PI 17/01287). A.F. received a fellowship from Xunta de Galicia (Plan I2C-2014). The CiMUS is supported by the Xunta de Galicia (2016–2019, ED431G/05). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIIIS