Hibernating brown bears are protected against atherogenic dyslipidemia.
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ABSTRACT:
SUBMITTER: Giroud S
PROVIDER: S-EPMC8455566 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Brown bears hibernate throughout half of the year as a survival strategy to reduce energy consumption during prolonged periods with scarcity of food and water. Thyroid hormones are the major endocrine regulators of basal metabolic rate in humans. Therefore, we aimed to determine regulations in serum thyroid hormone levels in hibernation compared to the active state to investigate if these are involved in the adaptions for hibernation.We used electrochemiluminescence immunoassay to quantify total triiodothyronine (T3) and thyroxine (T4) levels in hibernation and active state in paired serum samples from six subadult Scandinavian brown bears. Additionally, we determined regulations in the liver mRNA levels of three major thyroid hormone-binding proteins; thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin, by analysis of previously published grizzly bear RNA sequencing data.We found that bears were hypothyroid when hibernating with T4 levels reduced to less than 44% (P = 0.008) and T3 levels reduced to less than 36% (P = 0.016) of those measured in the active state. In hibernation, mRNA levels of TBG and albumin increased to 449% (P = 0.031) and 121% (P = 0.031), respectively, of those measured in the active state. TTR mRNA levels did not change.Hibernating bears are hypothyroid and share physiologic features with hypothyroid humans, including decreased basal metabolic rate, bradycardia, hypothermia, and fatigue. We speculate that decreased thyroid hormone signaling is a key mediator of hibernation physiology in bears. Our findings shed light on the translational potential of bear hibernation physiology to humans for whom a similar hypometabolic state could be of interest in specific conditions.
| S-EPMC9890737 | biostudies-literature
Project description:In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear's peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.
| S-EPMC7681968 | biostudies-literature
Project description:In this article, we present mass-spectrometry based plasma proteomics data from hibernating and active free-ranging Scandinavian brown bears (Ursus arctos). The brown bear hibernates for half the year. Despite obesity when entering the den and the prolonged period of inactivity, the bear shows no signs of the harmful effects associated with these conditions in humans. Thus, the hibernating bear is a potential translational model for addressing these complications in humans. We analyzed plasma samples from fourteen 2- to 3-year-old bears (6 males and 8 females) collected both during hibernation and the active state, and for some of the bears during two seasons, resulting in a total of 38 analyzed plasma samples. In triplicates, the plasma proteins were unfolded and reduced. To increase the chance of detecting low-molecular-weight proteins and peptides, we filtered the samples using a 50 K molecular weight cut-off filter with the aim to deplete larger abundant proteins, including albumin, and thereby increase the depth of the analysis. The proteins in the permeate were then tryptically digested, desalted, and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein identification and quantification was performed with the MaxQuant software searching against an Ursus arctos horribilis protein database. Here, we provide the raw data, a list with identified proteins in the plasma samples, and the databases applied for protein identification. Based on the provided data, differentially expressed proteins in hibernation compared to active state can be identified. These proteins may be involved in the bears' adaptions to hibernation physiology and hold potential as novel therapeutic targets.
| S-EPMC8873540 | biostudies-literature
Project description:ObjectivesComplex physiological adaptations often involve the coordination of molecular responses across multiple tissues. Establishing transcriptomic resources for non-traditional model organisms with phenotypes of interest can provide a foundation for understanding the genomic basis of these phenotypes, and the degree to which these resemble, or contrast, those of traditional model organisms. Here, we present a one-of-a-kind gene expression dataset generated from multiple tissues of two hibernating brown bears (Ursus arctos).Data descriptionThis dataset is comprised of 26 samples collected from 13 tissues of two hibernating brown bears. These samples were collected opportunistically and are typically not possible to attain, resulting in a highly unique and valuable gene expression dataset. In combination with previously published datasets, this new transcriptomic resource will facilitate detailed investigation of hibernation physiology in bears, and the potential to translate aspects of this biology to treat human disease.
| S-EPMC10251632 | biostudies-literature
Project description:During six months of annual hibernation, the brown bear undergoes unique physiological changes to adapt to decreased metabolic rate. We compared cardiac structural and functional measures of hibernating and active bears using comprehensive echocardiography. We performed echocardiography on 13 subadult free-ranging, anaesthetised Scandinavian brown bears (Ursus arctos) during late hibernation and in early summer. Mean heart rate was 26 beats per minute (standard deviation (SD): 8) during hibernation vs 71 (SD: 14) during active state. All left ventricular (LV) systolic and diastolic measures were decreased during hibernation: mean ejection fraction: 44.2% (SD: 6.0) active state vs 34.0 (SD: 8.1) hibernation, P?=?0.001; global longitudinal strain: -11.2% (SD: 2.0) vs -8.8 (SD: 3.3), P?=?0.03; global longitudinal strain rate: -0.82 (SD: 0.15) vs -0.41 (SD: 0.18), P?<?0.001; septal e': 9.8?cm/s (SD: 1.8) vs 5.2 (SD: 2.7), P?<?0.001. In general, measures of total myocardial motion (ejection fraction and global longitudinal strain) were decreased to a lesser extent than measures of myocardial velocities. In the hibernating brown bear, cardiac adaptation included decreased functional measures, primarily measures of myocardial velocities, but was not associated with cardiac atrophy. Understanding the mechanisms of these adaptations could provide pathophysiological insight of human pathological conditions such as heart failure.
| S-EPMC6959366 | biostudies-literature
Project description:Male and female 2- and 3-years old brown bear from the region of Tackasen (Sweden) were captured in summer and winter. Muscle biopsies from vastus lateralis were collected in february (hibernation state) and june (active period). Total RNA were extracted from muscle tissue and full transcriptome analysis (RNA Seq) were performed. Statistical analysis were performed to winter versus summer comparison from matched paired samples
2021-09-01 | GSE144856 | GEO
Project description:Oxidative stress, which is believed to promote muscle atrophy, has been reported to occur in a few hibernators. However, hibernating bears exhibit efficient energy savings and muscle protein sparing, despite long-term physical inactivity and fasting. We hypothesized that the regulation of the oxidant/antioxidant balance and oxidative stress could favor skeletal muscle maintenance in hibernating brown bears. We showed that increased expressions of cold-inducible proteins CIRBP and RBM3 could favor muscle mass maintenance and alleviate oxidative stress during hibernation. Downregulation of the subunits of the mitochondrial electron transfer chain complexes I, II, and III, and antioxidant enzymes, possibly due to the reduced mitochondrial content, indicated a possible reduction of the production of reactive oxygen species in the hibernating muscle. Concomitantly, the upregulation of cytosolic antioxidant systems, under the control of the transcription factor NRF2, and the maintenance of the GSH/GSSG ratio suggested that bear skeletal muscle is not under a significant oxidative insult during hibernation. Accordingly, lower levels of oxidative damage were recorded in hibernating bear skeletal muscles. These results identify mechanisms by which limited oxidative stress may underlie the resistance to skeletal muscle atrophy in hibernating brown bears. They may constitute therapeutic targets for the treatment of human muscle atrophy.
| S-EPMC6770786 | biostudies-literature
Project description:Understanding hibernation in brown bears (Ursus arctos) can provide insight into some human diseases. During hibernation, brown bears experience periods of insulin resistance, physical inactivity, extreme bradycardia, obesity, and the absence of urine production. These states closely mimic aspects of human diseases such as type 2 diabetes, muscle atrophy, as well as renal and heart failure. The reversibility of these states from hibernation to active season enables the identification of mediators with possible therapeutic value for humans. Recent studies have identified genes and pathways that are differentially expressed between active and hibernation seasons in bears. However, little is known about the role of differential expression of gene isoforms on hibernation physiology. To identify both distinct and novel mRNA isoforms, full-length RNA-sequencing (Iso-Seq) was performed on adipose, skeletal muscle, and liver from three individual bears sampled during both active and hibernation seasons. The existing reference genome annotation was improved by combining it with the Iso-Seq data. Short-read RNA-sequencing data from six individuals were mapped to the new reference annotation to quantify differential isoform usage (DIU) between tissues and seasons. We identified differentially expressed isoforms in all three tissues, to varying degrees. Adipose had a high level of DIU with isoform switching, regardless of whether the genes were differentially expressed. Our analyses revealed that DIU, even in the absence of differential gene expression, is an important mechanism for modulating genes during hibernation. These findings demonstrate the value of isoform expression studies and will serve as the basis for deeper exploration into hibernation biology.
| S-EPMC9210309 | biostudies-literature
Project description:Here we provide mass-spectrometry based plasma proteomics data of hibernating and active wild Scandinavian brown bears (Ursus arctos arctos). The brown bear hibernates for half the year. Despite obesity and the prolonged period of inactivity, bears show no signs of the harmful effects associated with these conditions in humans. Thus, the hibernating bear is a protentional translational model for addressing these complications in humans. We analyzed plasma samples from 14 subadult 2- to 3-year-old (y/o) bears (6 males and 8 females) collected both during hibernation and active state, and for some for the bears during two seasons, resulting in a total of 38 analyzed plasma samples. In triplicates, the proteins in the plasma samples were unfolded and reduced. To increase depth of the analysis and the chance to detect low molecular weight proteins and peptides, we filtered samples with a 50K MWCO filter with the aim to deplete larger proteins. The proteins in the permeate were then tryptically digested, desalted, and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein identification and quantification was performed with the MaxQuant software searching against an Ursus arctos horribilis protein database.
2021-12-21 | PXD030482 | Pride
Project description:BackgroundDespite 5-7 months of physical inactivity during hibernation, brown bears (Ursus arctos) are able to cope with physiological conditions that would be detrimental to humans. During hibernation, the tissue metabolic demands fall to 25% of the active state. Our objective was to assess cardiac function associated with metabolic depression in the hibernating vs. active states in free-ranging Scandinavian brown bears.MethodsWe performed echocardiography on seven free-ranging brown bears in Dalarna, Sweden, anesthetized with medetomidine-zolazepam-tiletamine-ketamine during winter hibernation in February 2013 and with medetomidine-zolazepam-tiletamine during active state in June 2013. We measured cardiac output noninvasively using estimates of hemodynamics obtained by pulsed wave Doppler echocardiography and 2D imaging. Comparisons were made using paired T-tests.ResultsDuring hibernation, all hemodynamic indices were significantly decreased (hibernating vs. active state): mean heart rate was 26.0 (standard deviation (SD): 5.6) beats per min vs. 75.0 (SD: 17.1) per min (P=0.002), mean stroke volume 32.3 (SD: 5.2) ml vs. 47.1 (SD: 7.9) ml (P=0.008), mean cardiac output 0.86 (SD: 0.31) l/min vs. 3.54 (SD: 1.04) l/min (P=0.003), and mean cardiac index 0.63 (SD: 0.21) l/min/kg vs. 2.45 (SD: 0.52) l/min/ m2 (P<0.001). Spontaneous echo contrast was present in all cardiac chambers in all seven bears during hibernation, despite the absence of atrial arrhythmias and valvular disease.ConclusionFree-ranging brown bears demonstrate hemodynamics comparable to humans during active state, whereas during hibernation, we documented extremely low-flow hemodynamics. Understanding these physiological changes in bears may help to gain insight into the mechanisms of cardiogenic shock and heart failure in humans.
| S-EPMC4245199 | biostudies-literature