Many small mammals and birds have developed specific mechanisms of energy saving, achieved by active and controlled reduction of metabolic rate (MR) and hence body temperature (Tb), i.e. torpor and hibernation [1]. The state of torpor involves controlled and tight regulations within the organism of many bodily systems (for a recent review, see [2]). However, despite two centuries of research on torpor, physiological mechanisms that regulate this overwintering strategy are still poorly understood. Polyunsaturated fatty acids (PUFA) are one of the main factors affecting torpor and hibernation performance. Heterothermic mammals fed diets containing plant oils that are rich in n-6 PUFA, notably linoleic acid (LA, C18:2 n-6), show a higher propensity of torpor use, lengthen their torpor bout duration, lower their minimum Tb and hence increase their energy savings (for review, see [3]). Conversely, there are evidences for adverse effects of n-3 PUFA on hibernation performance [4,5]. The heart plays a pivotal role in maintaining the body homeostasis, and its activity and metabolism are tightly regulated during torpor [6,7]. As previously hypothesized [8], the well-known influence of PUFA may be mediated via effects of the membrane fatty acid composition on the sarcoplasmic reticulum (SR) calcium ATPase (SERCA) in the heart of hibernators. This trans-membrane pump is responsible for removing calcium into the SR and hence for continued cardiac function even at extremely low Tb in torpor. We tested the hypotheses that high proportions of n-6 PUFA in general, or specifically high levels of LA, in SR phospholipids (PL) are associated with increased cardiac SERCA activity, and allow animals to reach lower minimum Tb in torpor. SERCA activity and SR PL fatty acid composition were assessed from hearts of hibernating and non-hibernating Syrian hamsters (Mesocricetus auratus), a granivorous, food-storing hibernator, and of hibernating garden dormice (Eliomys quercinus), an insectivorous, fat-storing hibernator. In both species, we found that SERCA activity was strongly up-regulated by increased proportion of LA in SR PL, but was negatively affected by the content of docosahexaenoic acid (DHA; C22:6 n-3) [9,10]. In hibernating hamsters, high levels of LA and low proportions of DHA were found in SR PL [9]. As a result, SERCA activity was significantly higher during entrance into torpor and in torpor compared to inter-bout arousal, i.e. phase of high MR and euthermic Tb between two torpor bouts. A subgroup of hamsters, which never entered torpor but remained euthermic throughout winter, displayed a phenotype similar to animals in summer, i.e. lower levels of LA and increased proportions of DHA in SR membranes [9]. Similarly, a group of dormice, which delayed their mean onset of hibernation by almost 4 days (range 0-12 days), showed extremely high levels of DHA prior to hibernation [10]. Both hamsters and dormice with increased SERCA activities reached lower Tb during torpor [9,10]. Interestingly, SERCA activity in torpor was three-times higher in garden dormice than in Syrian hamsters at similar DHA proportions in SR PL [10]. We conclude that (1) fatty acid composition of SR membranes modulates cardiac SERCA activity, hence determining the minimum Tb tolerated by hibernators, and (2) high DHA levels prevent hibernators from entering into torpor, but the critical levels differ substantially between species. These specific roles of PUFA in regulating key organs, such as the heart, hence body homeostasis during torpor and hibernation might shade light on the possibility for humans to enter a hibernation-like state for long-term space travels.