Genetic Control of Carbon Utilization During Hibernation: Mechanistic Considerations

Squire, Teresa L.; Andrews, Matthew T.

doi:10.1007/978-3-662-04162-8_35

Cited by 4 publications

(5 citation statements)

References 40 publications

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“…6) showing how changes in serum insulin and fatty acid levels regulate PDK4 expression and ultimately the switch from carbohydrate-to fatbased catabolism during hibernation. Figure 6 extends our previous model (27) on the regulation of genes controlling metabolism during hibernation and is based on results reported in this paper and recent experimental findings described in the following paragraphs.…”

Section: Discussionsupporting

confidence: 74%

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Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal

Buck

Squire

Andrews

2002

Physiological Genomics

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139

123

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Hibernation in mammals requires a metabolic shift away from the oxidation of carbohydrates and toward the combustion of stored fatty acids as the primary source of energy during torpor. A key element involved in this fuel selection is pyruvate dehydrogenase kinase isoenzyme 4 (PDK4). PDK4 inhibits pyruvate dehydrogenase and thus minimizes carbohydrate oxidation by preventing the flow of glycolytic products into the tricarboxylic acid cycle. This paper examines expression of the PDK4 gene during hibernation in heart, skeletal muscle, and white adipose tissue (WAT) of the 13-lined ground squirrel, Spermophilus tridecemlineatus. During hibernation PDK4 mRNA levels increase 5-fold in skeletal muscle and 15-fold in WAT compared with summer-active levels. Similarly, PDK4 protein is increased threefold in heart, fivefold in skeletal muscle, and eightfold in WAT. High levels of serum insulin, likely to have an inhibitory effect on PDK4 gene expression, are seen during fall when PDK4 mRNA levels are low. Coordinate upregulation of PDK4 in three distinct tissues suggests a common signal that regulates PDK4 expression and fuel selection during hibernation.

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Section: Discussionsupporting

confidence: 74%

“…Of key importance to hibernation is the potential role of PPAR␣ in coordinating PDK4 gene expression with the expression of genes responsible for extracellular and intracellular lipid transport and mitochondrial ␤-oxidation of fatty acids (reviewed in Ref. 27). As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal

Buck

Squire

Andrews

2002

Physiological Genomics

Self Cite

139

123

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“…WBC has been reported to either decline the GSH : GSSG ratio [ 16 ] or have no impact on it, depending on the time of exposure, number of sessions, and temperature declined. The increased activity of GR after cryogenic temperature exposure is correlated with GSH concentration, which is necessary for GST and GPx activity [ 32 ]. In the presented study, the increased activity of glutathione reductase, glutathione peroxidase, and superoxide dismutase after 5 and 10 cryosessions at −60°C shows that this temperature was significantly more beneficial for the induction of adaptive changes in the antioxidant system compared with lower temperatures (−90°C).…”

Section: Discussionmentioning

confidence: 99%

Effect of Whole-Body Cryotherapy on Antioxidant Systems in Experimental Rat Model

Skrzep-Poloczek

Romuk

Wiśnowiska³

et al. 2017

Oxidative Medicine and Cellular Longevity

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Background. The purpose of this study was to verify the effect of whole-body cryotherapy (WBC) in rats on their antioxidant systems, lipid peroxidation products, and their total oxidative status at different exposure times and temperatures. Methods. Antioxidants in serum, plasma, liver, and erythrocytes were evaluated in two study groups following 1 min of exposure to −60°C and −90°C, for 5 and 10 consecutive days. Results. WBC increased the activity of superoxide dismutase, catalase in the group subjected to 5 and 10 days exposure, −60°C. The glutathione S-transferase activity increased in the groups subjected to 10 days WBC sessions. Total antioxidant capacity increased after 5 and 10 days of 1 min WBC, −60°C; a decrease was observed at −90°C. A decreased level of erythrocyte malondialdehyde concentration was observed at −60°C after 5 and 10 days of cryostimulation. An increased concentration was measured at −90°C after 10 days, and increase of erythrocyte malondialdehyde concentration after 5 days, −90°C. Conclusions. To the best of our knowledge, this is the first research showing the effect of WBC in rats at different exposure times and temperatures. The effect of cryotherapy on enzymatic and nonenzymatic antioxidant systems was observed in the serum of animals exposed to a temperature of −60°C in comparison to control.

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“…Of potential importance to hibernation is the role of PPAR␣ in coordinating PDK4 gene expression with the expression of genes responsible for extracellular and intracellular lipid transport and mitochondrial ␤-oxidation of fatty acids (reviewed in Ref. 221). Activation of PPAR␣ could therefore provide a mechanism linking the inhibition of carbohydrate oxidation with increased fat catabolism, thus accounting for the switch in fuel selection during hibernation.…”

Section: B Shifts In Fuel Utilizationmentioning

confidence: 99%

Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

Carey

Andrews

Martin

2003

Physiological Reviews

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961

955

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Mammalian hibernators undergo a remarkable phenotypic switch that involves profound changes in physiology, morphology, and behavior in response to periods of unfavorable environmental conditions. The ability to hibernate is found throughout the class Mammalia and appears to involve differential expression of genes common to all mammals, rather than the induction of novel gene products unique to the hibernating state. The hibernation season is characterized by extended bouts of torpor, during which minimal body temperature (Tb) can fall as low as -2.9 degrees C and metabolism can be reduced to 1% of euthermic rates. Many global biochemical and physiological processes exploit low temperatures to lower reaction rates but retain the ability to resume full activity upon rewarming. Other critical functions must continue at physiologically relevant levels during torpor and be precisely regulated even at Tb values near 0 degrees C. Research using new tools of molecular and cellular biology is beginning to reveal how hibernators survive repeated cycles of torpor and arousal during the hibernation season. Comprehensive approaches that exploit advances in genomic and proteomic technologies are needed to further define the differentially expressed genes that distinguish the summer euthermic from winter hibernating states. Detailed understanding of hibernation from the molecular to organismal levels should enable the translation of this information to the development of a variety of hypothermic and hypometabolic strategies to improve outcomes for human and animal health.

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Genetic Control of Carbon Utilization During Hibernation: Mechanistic Considerations

Cited by 4 publications

References 40 publications

Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal

Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal

Effect of Whole-Body Cryotherapy on Antioxidant Systems in Experimental Rat Model

Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

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