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,
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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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    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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