Modulation of gene expression in heart and liver of hibernating black bears (Ursus americanus)

Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.
BMC Genomics (Impact Factor: 3.99). 03/2011; 12(1):171. DOI: 10.1186/1471-2164-12-171
Source: PubMed


Hibernation is an adaptive strategy to survive in highly seasonal or unpredictable environments. The molecular and genetic basis of hibernation physiology in mammals has only recently been studied using large scale genomic approaches. We analyzed gene expression in the American black bear, Ursus americanus, using a custom 12,800 cDNA probe microarray to detect differences in expression that occur in heart and liver during winter hibernation in comparison to summer active animals.
We identified 245 genes in heart and 319 genes in liver that were differentially expressed between winter and summer. The expression of 24 genes was significantly elevated during hibernation in both heart and liver. These genes are mostly involved in lipid catabolism and protein biosynthesis and include RNA binding protein motif 3 (Rbm3), which enhances protein synthesis at mildly hypothermic temperatures. Elevated expression of protein biosynthesis genes suggests induction of translation that may be related to adaptive mechanisms reducing cardiac and muscle atrophies over extended periods of low metabolism and immobility during hibernation in bears. Coordinated reduction of transcription of genes involved in amino acid catabolism suggests redirection of amino acids from catabolic pathways to protein biosynthesis. We identify common for black bears and small mammalian hibernators transcriptional changes in the liver that include induction of genes responsible for fatty acid β oxidation and carbohydrate synthesis and depression of genes involved in lipid biosynthesis, carbohydrate catabolism, cellular respiration and detoxification pathways.
Our findings show that modulation of gene expression during winter hibernation represents molecular mechanism of adaptation to extreme environments.

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Available from: Vadim B Fedorov, Oct 07, 2015
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    • "The array data were transformed with quantile normalization (Bolstad et al. 2003), and a one-way ANOVA test was used to select genes that exhibited significant differences between hibernating and summer-active animals. Similar to experiments with other tissues (Fedorov et al. 2011), a P-value <0.05 and |log 2 FC | >0.5 were set as cut-offs for significant differences in expressed genes, where FC is fold change (the mean expression value in the hibernating animals divided by the mean expression value in the summer-active animals as the criteria for differentially expressed genes as previously reported for other tissues (Fedorov et al. 2009, 2011)). The false discovery rate (FDR) was calculated using random permutation as described by Storey & Tibshirani (2003). "
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    ABSTRACT: Hibernation is an energy saving adaptation that involves a profound suppression of physical activity that can continue for 6-8 months in highly seasonal environments. While immobility and disuse generate muscle loss in most mammalian species, in contrast, hibernating bears and ground squirrels demonstrate limited muscle atrophy over the prolonged periods of physical inactivity during winter suggesting that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional programs that underlie molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screen in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels using custom 9,600 probe cDNA microarrays. A molecular pathway analysis showed an elevated proportion of over-expressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during torpor of hibernation that suggests induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through the prolonged periods of immobility of hibernation. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiple genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation.This article is protected by copyright. All rights reserved.
    Molecular Ecology 11/2014; 23:5524-5537. DOI:10.1111/mec.12963 · 6.49 Impact Factor
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    • "Changes in protein levels may also be due to either decreased excretion, associated with anuria in bears [66], or increased secretion of proteins into the serum. To this end, the differential expression of some serum protein genes in the liver of hibernating black bears have been reported, including α2-HS-glycoprotein, clusterin, and α2-macroglobulin [17], [67]. Future studies should be designed to elucidate the mechanisms underlying these serum proteome changes in hibernating black bears. "
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    ABSTRACT: Hibernation is an adaptation to conserve energy in the face of extreme environmental conditions and low food availability that has risen in several animal phyla. This phenomenon is characterized by reduced metabolic rate (∼25% of the active basal metabolic rate in hibernating bears) and energy demand, while other physiological adjustments are far from clear. The profiling of the serum proteome of the American black bear (Ursus americanus) may reveal specific proteins that are differentially modulated by hibernation, and provide insight into the remarkable physiological adaptations that characterize ursid hibernation. In this study, we used differential gel electrophoresis (DIGE) analysis, liquid chromatography coupled to tandem mass spectrometry, and subsequent MASCOT analysis of the mass spectra to identify candidate proteins that are differentially expressed during hibernation in captive black bears. Seventy serum proteins were identified as changing by ±1.5 fold or more, out of which 34 proteins increased expression during hibernation. The majority of identified proteins are involved in immune system processes. These included α2-macroglobulin, complement components C1s and C4, immunoglobulin μ and J chains, clusterin, haptoglobin, C4b binding protein, kininogen 1, α2-HS-glycoprotein, and apoplipoproteins A-I and A-IV. Differential expression of a subset of these proteins identified by proteomic analysis was also confirmed by immunodetection. We propose that the observed serum protein changes contribute to the maintenance of the hibernation phenotype and health, including increased capacities for bone maintenance and wound healing during hibernation in bears.
    PLoS ONE 06/2013; 8(6):e66119. DOI:10.1371/journal.pone.0066119 · 3.23 Impact Factor
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    • "It is well known that hibernators show seasonal changes in hepatic lipogenic activity. During hibernation , hepatic lipogenic activity was suppressed, which was inferred from a reduction in enzyme activities and gene expressions of key metabolic enzymes in ground squirrels (Wang et al. 1997; Yan et al. 2008) and American black bears (Fedorov et al. 2011). However, these studies mainly focused on the differences between the active and the hibernation phases. "
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    ABSTRACT: Body fat accumulation in the prehibernation period is crucial for survival and reproduction during hibernation for bears. Bear body mass increases rapidly during their autumnal hyperphagia phase, which is attributed not only to an increase in food availability, but also to physiological changes in lipid metabolism. To test this hypothesis, we investigated changes in blood biochemical values and mRNA expression levels of hepatic genes involved in lipid metabolism during the active period (June, August, October, and November) in Japanese black bears (Ursus thibetanus japonicus Schlegel, 1857), which were fed a constant ration throughout this period. Blood biochemical analysis revealed that plasma triglyceride concentrations decreased in October and November, implying that peripheral triglyceride uptake was accelerated in autumn. The liver was sampled by needle biopsy. Real-time polymerase chain reaction (PCR) analysis revealed that mRNA expressions of enzymes involved in glycolysis (glucokinase), as well as fatty acid and triglyceride synthesis (ATP-citrate lyase, acetyl-CoA carboxykinase 1, fatty acid synthase, and diacylglycerol O-acyltransferase 2), increased in November, which suggests that hepatic lipogenesis becomes accelerated during the hyperphagia phase. These results suggest that lipid metabolism is seasonally controlled even without changes in food intake. These physiological changes seen in the prehibernation period would contribute to the rapid mass gain necessary for hibernation.
    Canadian Journal of Zoology 07/2012; 90(8):945-954. DOI:10.1139/z2012-062 · 1.30 Impact Factor
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