The development of sustained, long-term endothermy was one of the major transitions in the evolution of vertebrates. Thermogenesis in endotherms does not only occur via shivering or activity, but also via non-shivering thermogenesis (NST). Mammalian NST is mediated by the uncoupling protein 1 in the brown adipose tissue (BAT) and possibly involves an additional mechanism of NST in skeletal muscle. This alternative mechanism is based on Ca 2+ -slippage by a sarcoplasmatic reticulum Ca 2+ -ATPase (SERCA) and is controlled by the protein sarcolipin. The existence of muscle based NST has been discussed for a long time and is likely present in all mammals. However, its importance for thermoregulation was demonstrated only recently in mice. Interestingly, birds, which have evolved from a different reptilian lineage than mammals and lack UCP1-mediated NST, also exhibit muscle based NST under the involvement of SERCA, though likely without the participation of sarcolipin. In this review we summarize the current knowledge on muscle NST and discuss the efficiency of muscle NST and BAT in the context of the hypothesis that muscle NST could have been the earliest mechanism of heat generation during cold exposure in vertebrates that ultimately enabled the evolution of endothermy. We suggest that the evolution of BAT in addition to muscle NST was related to heterothermy being predominant among early endothermic mammals. Furthermore, we argue that, in contrast to small mammals, muscle NST is sufficient to maintain high body temperature in birds, which have enhanced capacities to fuel muscle NST by high rates of fatty acid import.

Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis - features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD.

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According to the literature the steady-state level of phosphocreatine (PCr) has a linear relationship to the workload during muscle exercise intensities below the lactate threshold, whereas this linearity is impaired during exercise intensities above the lactate threshold. The purpose of this study was to investigate the linearity between PCr kinetics and workload during two bouts of isotonic incremental calf exercise with transitions from moderate- to high-intensity as well as from high- to moderate-intensity work rates. Using a whole-body 1.5 T MR scanner and a self-built exercise bench, we performed serial phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) with a time resolution of 30 s in nine healthy male volunteers. Changes in PCr, inorganic phosphate (Pi) and pH were statistically evaluated in comparison to the baseline. The exercise protocol started with a 4.5 W interval of 6 min followed by two bouts of 1.5 W increments. The workload was increased in 2-min intervals up to 9 W during the first bout and up to 7.5 W during the second bout. The second bout was preceded by a 4.5 W interval of 2 min and followed by a 4.5 W interval of 4 min. PCr hydrolysis achieved a steady state during each increment and was highly linear to the work rate (r (2), -0.796; P <0.001). Pi accumulated during each bout, whereas the pH decreased continuously during the first bout and did not exhibit any substantial decrease during the second bout. The metabolite levels and pH were expressed as the median value and the range. Our study confirms that steady-state PCr levels also have a linear relationship to work intensities above the lactate threshold, while pH changes do not have any impact on PCr degradation. The lack of substantial changes in pH during the second exercise bout indicates that prior high-intensity exercise leads to an activation of oxidative phosphorylation.