Behavioural mechanisms affecting energy regulation in mice prone or resistant to diet-induced obesity

We investigated inbred SWR/J and AKR/J mice, two established models for different susceptibility to dietinduced obesity (DIO), to scrutinize the contribution of physical activity and energy assimilation to the etiology of developing obesity. Body mass gain and body composition of mice fed a high-energy (HE) or a low caloric control diet were monitored. In parallel, assimilated energy, locomotor activity and thermoregulatory behaviour were measured. Activity was continuously registered by radio telemetry and, in addition, Open Field (OF) behaviour was used as a quick screening tool for spontaneous activity before and after the feeding trial. Energy assimilation was increased in both strains on HE (AKR/J: +60.7% and SWR/J: +42.8%) but only in AKR/J, body mass (+8.1%) and fat mass (+40.7%) were significantly elevated. As a trend, total home cage activity was increased and was more scattered in SWR/J. Interestingly, HE stimulated of activity only in SWR/J in the second trial at the end of the feeding experiment. The spatial pattern of OF activity also differed between strains with obese mice avoiding the core area. Under housing conditions, nest building behaviour was more pronounced in AKR/J. To further evaluate OF behaviour as a marker for spontaneous activity an obese mouse line was investigated. Mice lacking the leptin receptor (db/db) showed already before the onset of obesity lowest activity levels in OF. Adjustment of energy intake, higher activity levels and energy consuming thermoregulatory behaviour are mechanisms employed by SWR/J mice to dissipate excess energy as a defence against the onset of obesity. Therefore our results deciphering mechanisms of DIO-sensitivity in mice contribute to the understanding of inter-individual differences in body weight development in an adipogenic environment

5 '-AMP impacts lymphocyte recirculation through activation of A(2B) receptors

<p>Natural hibernation consists of torpid phases with metabolic suppression alternating with euthermic periods. Induction of torpor holds substantial promise in various medical conditions, including trauma, major surgery, and transplantation. Torpor in mice can be induced pharmacologically by 5-AMP. Previously, we showed that during natural torpor, the reduction in body temperature results in lymphopenia via a reduction in plasma S1P. Here, we show that during torpor induced by 5-AMP, there is a similar reduction in the number of circulating lymphocytes that is a result of their retention in secondary lymphoid organs. This lymphopenia could be mimicked by engagement of A(2B)Rs by a selective A(2B)R agonist (LUF6210) in the absence of changes in temperature and prevented by A(2B)R antagonists during 5-AMP-induced torpor. In addition, forced cooling of mice led to peripheral blood lymphopenia, independent of A(2B)R signaling. The induction of torpor using 5-AMP impacted the migration of lymphocytes within and between secondary lymphoid organs. During torpor, the homing into LNs was impaired, and two-photon intravital microscopy revealed that cell motility was decreased significantly and rapidly upon 5-AMP administration. Furthermore, the S1P plasma concentration was reduced by 5-AMP but not by LUF6210. S1P plasma levels restored upon arousal. Likely, the reduced migration in LNs combined with the reduced S1P plasma level substantially reduces lymphocyte egress after injection of 5-AMP. In conclusion, 5-AMP induces a state of pharmacological torpor in mice, during which, lymphopenia is governed primarily by body temperature-independent suppression of lymphocyte egress from LNs.</p>