Regulation of pyruvate dehydrogenase (PDH) in the hibernating ground squirrel, ( Ictidomys tridecemlineatus )

Wijenayake, Sanoji; Tessier, Shannon N.; Storey, Kenneth B.

doi:10.1016/j.jtherbio.2017.07.010

Cited by 28 publications

(17 citation statements)

References 36 publications

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“…The upregulation of PDK4 provides a molecular mechanism that accounts for suppression of genes involved in the PDH complex in WAT. These patterns of expression regarding the PDH complex have been seen in multiple tissues in ground squirrel species (Andrews et al, 1998;Buck et al, 2002;Wijenayake, Tessier, & Storey, 2017) and American black bears .…”

Section: The Pyruvate Dehydrogenase Complex Is Downregulated Duringmentioning

confidence: 77%

Transcriptomics in the wild: Hibernation physiology in free‐ranging dwarf lemurs

et al. 2018

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Hibernation is an adaptive strategy some mammals use to survive highly seasonal or unpredictable environments. We present the first investigation on the transcriptomics of hibernation in a natural population of primate hibernators: Crossley's dwarf lemurs (Cheirogaleus crossleyi). Using capture-mark-recapture techniques to track the same animals over a period of 7 months in Madagascar, we used RNA-seq to compare gene expression profiles in white adipose tissue (WAT) during three distinct physiological states. We focus on pathway analysis to assess the biological significance of transcriptional changes in dwarf lemur WAT and, by comparing and contrasting what is known in other model hibernating species, contribute to a broader understanding of genomic contributions of hibernation across Mammalia. The hibernation signature is characterized by a suppression of lipid biosynthesis, pyruvate metabolism and mitochondrial-associated functions, and an accumulation of transcripts encoding ribosomal components and iron-storage proteins. The data support a key role of pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) in regulating the shift in fuel economy during periods of severe food deprivation. This pattern of PDK4 holds true across representative hibernating species from disparate mammalian groups, suggesting that the genetic underpinnings of hibernation may be ancestral to mammals.

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Section: The Pyruvate Dehydrogenase Complex Is Downregulated Duringmentioning

confidence: 77%

Transcriptomics in the wild: Hibernation physiology in free‐ranging dwarf lemurs

et al. 2018

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“…Phosphorylation of pyruvate dehydrogenase (PDH) at S232, S293 or S300 by any of four PDK isozymes inhibits its activity (Harris, Bowker‐Kinley, Huang, & Wu, ) and is crucial for blocking the oxidation of pyruvate as a substrate, especially when carbohydrate reserves must be conserved. Indeed, strong suppression of PDH activity during hibernation has been widely reported in multiple tissues of eutherian hibernators (summarized in Wijenayake, Tessier, & Storey, ). Strong increases in PDH phosphorylation at 1, 2 or all 3 serine sites were also reported for six tissues (including brain, liver and skeletal muscle) of D. gliroides (Wijenayake et al., ) and the up‐regulation of PDK4 in brain (predictably elevating PDK4 protein) would support PDH inhibition and presumably help to direct brain to make greater use of ketones as substrates during hibernation.…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, strong suppression of PDH activity during hibernation has been widely reported in multiple tissues of eutherian hibernators (summarized in Wijenayake, Tessier, & Storey, ). Strong increases in PDH phosphorylation at 1, 2 or all 3 serine sites were also reported for six tissues (including brain, liver and skeletal muscle) of D. gliroides (Wijenayake et al., ) and the up‐regulation of PDK4 in brain (predictably elevating PDK4 protein) would support PDH inhibition and presumably help to direct brain to make greater use of ketones as substrates during hibernation.…”

Section: Discussionmentioning

confidence: 97%

A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation

et al. 2018

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The small South American marsupial, Dromiciops gliroides, known as the missing link between the American and the Australian marsupials, is one of the few South American mammals known to hibernate. Expressing both daily torpor and seasonal hibernation, this species may provide crucial information about the mechanisms and the evolutionary origins of marsupial hibernation. Here, we compared torpid and active individuals, applying high-throughput sequencing technologies (RNA-seq) to profile gene expression in three D. gliroides tissues and determine whether hibernation induces tissue-specific differential gene expression. We found 566 transcripts that were significantly up-regulated during hibernation (369 in brain, 147 in liver and 50 in skeletal muscle) and 339 that were down-regulated (225 in brain, 79 in liver and 35 in muscle). The proteins encoded by these differentially expressed genes orchestrate multiple metabolic changes during hibernation, such as inhibition of angiogenesis, prevention of muscle disuse atrophy, fuel switch from carbohydrate to lipid metabolism, protection against reactive oxygen species and repair of damaged DNA.According to the global enrichment analysis, brain cells seem to differentially regulate a complex array of biological functions (e.g., cold sensitivity, circadian perception, stress response), whereas liver and muscle cells prioritize fuel switch and heat production for rewarming. Interestingly, transcripts of thioredoxin-interacting protein (TXNIP), a potent antioxidant, were significantly over-expressed during torpor in all three tissues. These results suggest that marsupial hibernation is a controlled process where selected metabolic pathways show adaptive modulation that can help to maintain homeostasis and enhance cytoprotection in the hypometabolic state.

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“…Pyruvate dehydrogenase (PDH) connects glycolysis and the TCA cycle by converting pyruvate to acetyl-CoA ( Figure 3M). In hibernating animals, respiratory rate and oxygen consumption are markedly suppressed, and previous studies have indicated that PDH activity is downregulated during hibernation (Wijenayake et al, 2017). If 2MT indeed inhibits PDH activity, it is anticipated to suppress TCA cycle activity, as observed in hibernating animals.…”

Section: Mt Induces Crisis-response Metabolismmentioning

confidence: 93%

Thiazoline-related TRPA1 agonist odorants orchestrate survival fate in mice

Matsuo

Isosaka

Tang

et al. 2020

Preprint

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Regulation of pyruvate dehydrogenase (PDH) in the hibernating ground squirrel, ( Ictidomys tridecemlineatus )

Cited by 28 publications

References 36 publications

Transcriptomics in the wild: Hibernation physiology in free‐ranging dwarf lemurs

Transcriptomics in the wild: Hibernation physiology in free‐ranging dwarf lemurs

A functional transcriptomic analysis in the relict marsupial Dromiciops gliroides reveals adaptive regulation of protective functions during hibernation

Thiazoline-related TRPA1 agonist odorants orchestrate survival fate in mice

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