Effects of polyunsaturated fatty acids on hibernation and ageing
It is known that hibernators save energy by substantially decreasing metabolic rate and body temperature (Tb), but spend ~80% of their energy expenditure to repeatedly rewarm during winter. However, the function of these arousals remains a mystery. Dietary uptake of polyunsaturated fatty acids (PUFA), especially of Linoleic acid (LA, C18:2 n-6), strongly affects torpor duration and hence the frequency of arousals, suggesting a limiting effect of PUFA on the time individuals can remain torpid.
We hypothesize that high n-6 PUFA content in membrane phospholipids (PL) mitigates the effects of low temperature on the activity of the cardiac sarcoplasmic reticulum (SR) calcium ATPase (SERCA2a), the enzyme responsible for removing calcium into the SR and for proper cardiac function. Whereas protein degradation is not entirely blocked at low Tb, protein synthesis, including SERCA2a, is drastically down-regulated during torpor entrance and only resumed during arousals. A high LA content could partially compensate for a reduction in SERCA2a activity resulting from proteolysis over time, prolonging the time hibernators can remain torpid until the need to synthetize SERCA2a forces them to rewarm to euthermic Tb. The intake of LA may involve a trade-off, however, since extremely high LA levels above an apparent optimum trigger a decrease in hibernation. This could be due to increased PUFA-related oxidative damage during the torpor-arousal cycle, impacting negatively on SERCA2a activity and on somatic maintenance in general.
In view of these potential trade-offs, we are experimentally testing the following hypothetical concept, using dietary manipulation of LA intake:
Optimal levels of LA will enable hibernators to maintain high levels of SERCA2a activity. This in turn will lead to increased torpor duration, compared with animals on very low or extremely high LA diets. Individuals will re-synthesize SERCA2a during euthermic phases, leading to higher SERCA2a activity in early subsequent torpor, compared with later stages in a bout. An increase in membrane LA beyond optimal levels will lead to a rise in oxidative stress, affecting negatively SERCA2a activity, forcing individuals to rewarm more often and to lengthen their time spent euthermic. Frequent arousals will lead to increased levels of markers of oxidative stress, cellular damage, and accelerated ageing.
- Duration 1 September 2014-31 August 2017