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

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          Abstract

          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 (T b), 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) Ca 2+ ATPase 2 (SERCA2) and thus determine the threshold T b 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 T b 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 T b tolerated by hibernators, and (2) high DHA levels prevent hibernators from entering into torpor, but the critical levels differ substantially between species.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps.

            The role of ATP-dependent calcium uptake into intracellular storage compartments is an essential feature of hormonally induced calcium signaling. Thapsigargin, a non-phorboid tumor promoter, increasingly is being used to manipulate calcium stores because it induces a hormone-like elevation of cytosolic calcium. It has been suggested that thapsigargin acts through inhibition of the endoplasmic reticulum calcium pump. We have directly tested the specificity of thapsigargin on all of the known intracellular-type calcium pumps (referred to as the sarcoplasmic or endoplasmic reticulum Ca-ATPase family (SERCA]. Full-length cDNA clones encoding SERCA1, SERCA2a, SERCA2b, and SERCA3 enzymes were expressed in COS cells, and both calcium uptake and calcium-dependent ATPase activity were assayed in microsomes isolated from them. Thapsigargin inhibited all of the SERCA isozymes with equal potency. Furthermore, similar doses of thapsigargin abolished the calcium uptake and ATPase activity of sarcoplasmic reticulum isolated from fast twitch and cardiac muscle but had no influence on either the plasma membrane Ca-ATPase or Na,K-ATPase. The interaction of thapsigargin with the SERCA isoforms is rapid, stoichiometric, and essentially irreversible. These properties demonstrate that thapsigargin interacts with a recognition site found in, and only in, all members of the endoplasmic and sarcoplasmic reticulum calcium pump family.
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              Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis.

              Polyunsaturated fatty acids (PUFAs) can have strong effects on hibernation and daily torpor in mammals. High dietary PUFA contents were found to increase proneness for torpor, decrease body temperatures, prolong torpor bout duration, and attenuate hibernation mass loss. The mechanism by which PUFAs enhance torpor and hibernation is unknown, however. On the basis of a review of the literature, and on reexamining our own data on alpine marmots, we propose that effects on hibernation are not due to PUFAs in general, but to shifts in the ratio of n-6 PUFAs to n-3 PUFAs in membrane phospholipids. Specifically, high ratios of n-6 to n-3 PUFAs increase the activity of the Ca2+-Mg2+ pump in the sarcoplasmic reticulum of the heart (SERCA) and counteract Q10 effects on SERCA activity at low tissue temperatures. Therefore, high n-6 to n-3 PUFA ratios in cardiac myocyte membranes appear to protect the hibernating heart from arrhythmia, which in hypothermic nonhibernators is caused by massive increases in cytosolic Ca2+. The resulting reduced risk of cardiac arrest during hypothermia may explain why increased dietary uptake of n-6 PUFAs, but not of n-3 PUFAs, can strongly enhance the propensity for hibernation, and allows heterotherms to reach lower body temperatures, with associated increased energy savings. Therefore, at least for herbivorous hibernators, such as marmots, linoleic acid (C18:2 n-6)--the dietary source of all n-6 PUFAs--appears to represent a crucial and limited resource in natural environments.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                18 September 2018
                2018
                : 9
                : 1235
                Affiliations
                Department of Integrative Biology and Evolution, Research Institute of Wildlife Ecology, University of Veterinary Medicine , Vienna, Austria
                Author notes

                Edited by: David C. Randall, University of Kentucky College of Medicine, United States

                Reviewed by: Manuel Ramírez-Sánchez, Universidad de Jaén, Spain; Caroline Habold, UMR 7178, Institut Pluridisciplinaire Hubert Curien (IPHC), France

                *Correspondence: Sylvain Giroud, sylvain.giroud@ 123456vetmeduni.ac.at

                Present address: Jae Kwak, International Flavors & Fragrances, Inc., Union Beach, NJ, United States

                This article was submitted to Integrative Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2018.01235
                6153335
                30279661
                8e6a35ab-e472-4569-a74a-f01f275e6797
                Copyright © 2018 Giroud, Stalder, Gerritsmann, Kübber-Heiss, Kwak, Arnold and Ruf.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 May 2018
                : 15 August 2018
                Page count
                Figures: 4, Tables: 6, Equations: 0, References: 48, Pages: 12, Words: 0
                Funding
                Funded by: Austrian Science Fund 10.13039/501100002428
                Award ID: P27267-B25
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                fatty acids,pufa,linoleic acid,docosahexaenoic acid,torpor,hibernation,insectivorous
                Anatomy & Physiology
                fatty acids, pufa, linoleic acid, docosahexaenoic acid, torpor, hibernation, insectivorous

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