Membrane phospholipid fatty acid composition regulates cardiac SERCA activity in a hibernator, the Syrian hamster (<i>Mesocricetus auratus</i>)

Polyunsaturated fatty acids (PUFA) have strong effects on hibernation and daily torpor. Increased dietary uptake of PUFA of the n-6 class, particularly of Linoleic acid (LA, C18:2 n-6) lengthens torpor bout duration and enables animals to reach lower body temperatures (T-b) and metabolic rates. As previously hypothesized, this well-known influence of PUFA may be mediated via effects of the membrane fatty acid composition on sarcoplasmic reticulum (SR) Ca2+- ATPase 2a (SERCA) in the heart of hibernators. We tested the hypotheses that high proportions of n-6 PUFA in general, or specifically high proportions of LA (C18:2 n-6) in SR phospholipids (PL) should be associated with increased cardiac SERCA activity, and should allow animals to reach lower minimum T-b in torpor. We measured activity of SERCA from hearts of hibernating and non-hibernating Syrian hamsters (Mesocricetus auratus) in vitro at 35 degrees C. Further, we determined the PL fatty acid composition of the SR membrane of these hearts. We found that SERCA activity strongly increased as the proportion of LA in SR PL increased but was negatively affected by the content of Docosahexaenoic acid (DHA; C22:6 n-3). SR PL from hibernating hamsters were characterized by high proportions of LA and low proportions of DHA. As a result, SERCA activity was significantly higher during entrance into torpor and in torpor compared to inter-bout arousal. Also, animals with increased SERCA activity reached lower T-b during torpor. Interestingly, a subgroup of hamsters which never entered torpor but remained euthermic throughout winter displayed a phenotype similar to animals in summer. This was characterized by lower proportions of LA and increased proportions of DHA in SR membranes, which is apparently incompatible with torpor. We conclude that the PUFA composition of SR membranes affects cardiac function via modulating SERCA activity, and hence determines the minimum T-b tolerated by hibernators.</p

Seasonal Control of Mammalian Energy Balance : Recent advances in the understanding of daily torpor and hibernation

Funding This work was supported in part by BBSRC grant (BB/M001504/1) to PB, DFG Emmy-Noether HE6383 to AH, German Center for Diabetes Research (DZD) to MJ.Peer reviewedPostprin

Seasonal Control of Mammalian Energy Balance : Recent advances in the understanding of daily torpor and hibernation

Funding This work was supported in part by BBSRC grant (BB/M001504/1) to PB, DFG Emmy-Noether HE6383 to AH, German Center for Diabetes Research (DZD) to MJ.Peer reviewedPostprin

The Torpid State:Recent Advances in Metabolic Adaptations and Protective Mechanisms(dagger)

Torpor and hibernation are powerful strategies enabling animals to survive periods of low resource availability. The state of torpor results from an active and drastic reduction of an individual's metabolic rate (MR) associated with a relatively pronounced decrease in body temperature. To date, several forms of torpor have been described in all three mammalian subclasses, i.e., monotremes, marsupials, and placentals, as well as in a few avian orders. This review highlights some of the characteristics, from the whole organism down to cellular and molecular aspects, associated with the torpor phenotype. The first part of this review focuses on the specific metabolic adaptations of torpor, as it is used by many species from temperate zones. This notably includes the endocrine changes involved in fat- and food-storing hibernating species, explaining biomedical implications of MR depression. We further compare adaptive mechanisms occurring in opportunistic vs. seasonal heterotherms, such as tropical and sub-tropical species. Such comparisons bring new insights into the metabolic origins of hibernation among tropical species, including resistance mechanisms to oxidative stress. The second section of this review emphasizes the mechanisms enabling heterotherms to protect their key organs against potential threats, such as reactive oxygen species, associated with the torpid state. We notably address the mechanisms of cellular rehabilitation and protection during torpor and hibernation, with an emphasis on the brain, a central organ requiring protection during torpor and recovery. Also, a special focus is given to the role of an ubiquitous and readily-diffusing molecule, hydrogen sulfide (H2S), in protecting against ischemia-reperfusion damage in various organs over the torpor-arousal cycle and during the torpid state. We conclude that (i) the flexibility of torpor use as an adaptive strategy enables different heterothermic species to substantially suppress their energy needs during periods of severely reduced food availability, (ii) the torpor phenotype implies marked metabolic adaptations from the whole organism down to cellular and molecular levels, and (iii) the torpid state is associated with highly efficient rehabilitation and protective mechanisms ensuring the continuity of proper bodily functions. Comparison of mechanisms in monotremes and marsupials is warranted for understanding the origin and evolution of mammalian torpor

Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation

Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in freeranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alphalinolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolism

Elevated plasma phospholipid n-3 docosapentaenoic acid concentrations during hibernation

Factors for initiating hibernation are unknown, but the condition shares some metabolic similarities with consciousness/sleep, which has been associated with n-3 fatty acids in humans. We investigated plasma phospholipid fatty acid profiles during hibernation and summer in freeranging brown bears (Ursus arctos) and in captive garden dormice (Eliomys quercinus) contrasting in their hibernation patterns. The dormice received three different dietary fatty acid concentrations of linoleic acid (LA) (19%, 36% and 53%), with correspondingly decreased alphalinolenic acid (ALA) (32%, 17% and 1.4%). Saturated and monounsaturated fatty acids showed small differences between summer and hibernation in both species. The dormice diet influenced n-6 fatty acids and eicosapentaenoic acid (EPA) concentrations in plasma phospholipids. Consistent differences between summer and hibernation in bears and dormice were decreased ALA and EPA and marked increase of n-3 docosapentaenoic acid and a minor increase of docosahexaenoic acid in parallel with several hundred percent increase of the activity index of elongase ELOVL2 transforming C20-22 fatty acids. The highest LA supply was unexpectantly associated with the highest transformation of the n-3 fatty acids. Similar fatty acid patterns in two contrasting hibernating species indicates a link to the hibernation phenotype and requires further studies in relation to consciousness and metabolismpublishedVersio

Temperature effects on DNA damage during hibernation

During multiday torpor, deep-hibernating mammals maintain a hypometabolic state where heart rate and ventilation are reduced to 2%–4% of euthermic rates. It is hypothesized that this ischemia-like condition may cause DNA damage through reactive oxygen species production. The reason for intermittent rewarming (arousal) during hibernation might be to repair the accumulated DNA dam-age. Because increasing ambient temperatures (Ta’s) shortens torpor bout duration, we hypothesize that hibernating at higher Ta’swill result in a faster accumulation of genomic DNA damage. To test this, we kept 39 male and female garden dormice at a Ta of either 57C or 107C and obtained tissue at 1, 4, and 8 d in torpor to assess DNA damage and recruitment of DNA repair markers in splenocytes. DNA damage in splenocytes measured by comet assay was significantly higher in almost all torpor groups than in sum-mer euthermic groups. Damage accumulates in the first days of torpor at Ta = 57C (between days 1 and 4) but not at Ta = 107C. At the higher Ta, DNA damage is high at 24 h in torpor, indicating either a faster buildup of DNA damage at higher Ta’soranin-complete repair during arousals in dormice. At 57C, recruitment of the DNA repair protein 53BP1 paralleled the increase in DNA damage over time during torpor. In contrast, after 1 d in torpor at 107C, DNA damage levels were high, but 53BP1 was not re-cruited to the nuclear DNA yet. The data suggest a potential mis-match in the DNA damage/repair dynamics during torpor at higher Ta’s.</p

Seasonality in Biological Rhythms in Scandinavian brown Bears

Biological rhythms, such as rhythms in activity and body temperature, are usually highly synchronized and entrained by environmental conditions, such as photoperiod. However, how the expression of these rhythms changes during hibernation, when the perception of environmental cues is limited, has not yet been fully understood for all hibernators, especially in the wild. The brown bear (Ursus arctos) in Scandinavia lives in a highly seasonal environment and adapts to harsh winter conditions by exhibiting hibernation, characterized by reduced metabolism and activity. In this study, we aimed to explore the expression of biological rhythms in activity, body temperature and heart rate of free-ranging brown bears over the annual cycle, including active, hibernation and the transition states around den entry and exit. We found that rhythms in physiology and activity are mostly synchronized and entrained by the light-dark cycle during the bears’ active state with predominantly diel and ultradian rhythms for body temperature, activity, and heart rate. However, during hibernation, rhythms in body temperature and heart rate were considerably slowed down to infradian rhythms, influenced by the amount of snow in the denning area, whereas rhythms in activity remained diel. Rhythms in the transition states when bears prepared for entering or coming out of hibernation state displayed a combination of infradian and diel rhythms, indicating the preparation of the body for the change in environmental conditions. These results reveal that brown bears adjust their biological rhythms to the seasonal environment they inhabit. Rhythms in physiology and activity show simultaneity during the active state but are partly disconnected from each other during hibernation, when bears are most sheltered from the environment.publishedVersio

Dietary Lipids Affect the Onset of Hibernation in the Garden Dormouse (Eliomys quercinus): Implications for Cardiac Function

Dietary lipids strongly influence patterns of hibernation in heterotherms. Increased dietary uptake of n-6 polyunsaturated fatty acids (PUFAs), particularly of linoleic acid (LA, C18:2 n-6), enables animals to reach lower body temperatures (Tb), lengthens torpor bout duration, and results in lower energy expenditure during hibernation. Conversely, dietary n-3 PUFA impacts negatively on hibernation performance. PUFA in surrounding phospholipids (PLs) presumably modulate the temperature-dependent activity of the sarcoplasmic reticulum (SR) Ca2+ ATPase 2 (SERCA2) and thus determine the threshold Tb still allowing proper heart function during torpor. We tested the effect of diets enriched with 10% of either corn oil (“CO,” high n-6 PUFA, e.g., LA) or menhaden oil [“MO,” long-chain n-3 PUFA, e.g., docosahexaenoic acid (DHA)] on hibernation performance and SERCA2 activity levels during torpor in garden dormice, an insectivorous, fat-storing hibernator. Prior to hibernation, individuals fed the MO diet showed an almost nine-times higher DHA levels and 30% lower LA proportions in white adipose tissue (WAT), reflecting the fatty acid composition of SR membranes, compared to CO-diet fed animals. When fed the MO diet, dormice significantly delayed their mean onset of hibernation by almost 4 days (range: 0–12 days), compared with CO-diet fed animals. Hibernation onset correlated positively with WAT-DHA levels and negatively with WAT-LA proportions prior to hibernation. Subsequently, hibernating patterns were similar between the two dietary groups, despite a significant difference in WAT-LA but not in WAT-DHA levels in mid-hibernation. SR-PL fatty acid composition and SERCA2 activity were identical in torpid individuals from the two dietary groups in mid-hibernation. In line with our previous findings on Syrian hamsters, a granivorous, food-storing hibernator, SERCA2 activity correlated positively with LA and negatively with DHA levels of SR-PL in torpid dormice, although SERCA2 activity was about three-times higher in garden dormice than in Syrian hamsters at similar PL-DHA proportions. Similarly, minimal Tb during torpor decreased as SERCA2 activity increased. We conclude that: (1) fatty acid composition of SR membranes modulates cardiac SERCA2 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

Lipidomics reveals seasonal shifts in a large-bodied hibernator, the brown bear

publishedVersio