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Genes controlling the metabolic switch in hibernating mammals
1Department of Biology and Department of Biochemistry and Molecular Biology, University of Minnesota Duluth, Duluth, MN 55812, USA. mandrews@d.umn.edu
Hibernating mammals switch to fatty acid metabolism using pancreatic triacylglycerol lipase (PTL) activity at near-freezing temperatures. This adaptation allows survival without food during winter dormancy.
Area of Science:
- Physiology
- Metabolic Biochemistry
- Comparative Biology
Background:
- Hibernating mammals survive prolonged periods without food by drastically reducing metabolic rate and body temperature.
- This seasonal adaptation involves a shift in energy substrate utilization from carbohydrates to fatty acids.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the metabolic shift during mammalian hibernation.
- To examine the role of pyruvate dehydrogenase kinase isoenzyme 4 in regulating fuel selection.
- To assess the low-temperature activity of pancreatic triacylglycerol lipase (PTL) in hibernators.
Main Methods:
- Differential gene expression analysis of pyruvate dehydrogenase kinase isoenzyme 4 in hibernating ground squirrels.
- Biochemical assays of recombinant ground squirrel and human PTL activity at low temperatures (0-37°C).
- Measurement of oxygen consumption and heart rate in hibernating versus active states.
Main Results:
- Pyruvate dehydrogenase kinase isoenzyme 4 expression is differentially regulated, inhibiting carbohydrate oxidation.
- Pancreatic triacylglycerol lipase (PTL) from both ground squirrels and humans exhibits significant lipolytic activity at 0°C.
- PTL shows low temperature sensitivity (Q(10) = 1.2-1.5), indicating functional lipolysis during hibernation.
Conclusions:
- The metabolic shift in hibernators involves suppressed carbohydrate oxidation via pyruvate dehydrogenase kinase isoenzyme 4.
- Pancreatic triacylglycerol lipase (PTL) possesses intrinsic low-temperature activity, facilitating fatty acid mobilization during hibernation.
- This lipolytic capability is a general property of PTL and not dependent on unique hibernator-specific modifications.
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