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Metabolism of hepatocytes from a mammalian hibernator, Spermophilus lateralis

University of British Columbia

In mammalian hibernators, metabolism varies dramatically between deep hibernation and arousal. This change is reflected in tissue glycolytic and oxidative capacities. This thesis investigated cellular and tissue metabolism in the different stages of hibernation in ground squirrels. Total liver ATP content was not different between deep hibernation, arousal, and summer euthermia. In vivo 31P-NMR spectroscopy showed no change in liver and skeletal muscle high energy phosphate content during arousal. This observation indicates that metabolism is well regulated, and ATP consumption must be reduced to a similar degree as ATP production in hibernation. I predicted a reduced metabolic rate (Vo2) in hepatocytes isolated from animals in deep hibernation relative to cells from euthermic squirrels. At 37°C, Vo2 was 20% - 25% higher in hepatocytes from hibernating, aroused and summer cold acclimated animals than in cells from summer euthermic controls. Na+/K+ ATPase, considered an important ATP consumer in mammalian tissues, accounted for only around 15% of cellular Vo2 at 37°C, and this proportion did not change with hibernation state. When measured at 7°C, no difference in hepatocyte Vo2 was found between hibernation states. A CO2 induced intracellular acidification of 0.1 - 0.2 pH units did not affect Vo2 at 37°C or 7°C. I hypothesized that the higher metabolic capacities of hepatocytes from hibernating and aroused animals may permit higher rates of biosynthetic functions, important during periodic arousals. At 37°C gluconeogenic rates from lactate/pyruvate were 63% higher in hepatocytes from hibernating squirrels than those from summer control animals. With glycerol, these rates in the hibernating, aroused and cold acclimated states were twice that of summer state. No differences in activities of key gluconeogenic enzymes or oxidative efficiencies between hibernation states were found. Endogenous rates of ketone body production were higher in hepatocytes from hibernating S. lateralis, but with 3mM palmitate as substrate, no differences were evident. From these studies I conclude that metabolism remains well regulated, balanced and flexible throughout the hibernation cycle. This unique metabolice organization may permit energetic savings by allowing for a reduced Vb2 in deep hibernation, and an elevated VO2 during arousal to support high biosynthetic rates, thereby minimizing arousal durations and their attendant thermogenic demands.

Thesis/Dissertation

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2009-03-18

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http://hdl.handle.net/2429/6205

Zoology

University of British Columbia

UBCV

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