Abstract
To investigate mechanisms by which hibernators avoid atherogenic hyperlipidemia during hibernation, we assessed lipoprotein and cholesterol metabolisms of free-ranging Scandinavian brown bears (Ursus arctos). In winter- and summer-captured bears, we measured lipoprotein sizes and sub-classes, triglyceride-related plasma-enzyme activities, and muscle lipid composition along with plasma-levels of antioxidant capacities and inflammatory markers. Although hibernating bears increased nearly all lipid levels, a 36%-higher cholesteryl-ester transfer-protein activity allowed to stabilize lipid composition of high-density lipoproteins (HDL). Levels of inflammatory metabolites, i.e., 7-ketocholesterol and 11ß-prostaglandin F2α, declined in winter and correlated inversely with cardioprotective HDL2b-proportions and HDL-sizes that increased during hibernation. Lower muscle-cholesterol concentrations and lecithin-cholesterol acyltransferase activity in winter suggest that hibernating bears tightly controlled peripheral-cholesterol synthesis and/or release. Finally, greater plasma-antioxidant capacities prevented excessive lipid-specific oxidative damages in plasma and muscles of hibernating bears. Hence, the brown bear manages large lipid fluxes during hibernation, without developing adverse atherogenic effects that occur in humans and non-hibernators.
Highlights
To investigate mechanisms by which hibernators avoid atherogenic hyperlipidemia during hibernation, we assessed lipoprotein and cholesterol metabolisms of free-ranging Scandinavian brown bears (Ursus arctos)
In small (< 8 kg) hibernating species, hibernation corresponds to successive multi-days or -weeks torpor bouts, during which individual metabolic rate (‘MR’) is reduced on average by ~ 95% of basal rates with body temperature lowered below 10 °C, that are interspaced by euthermic phases lasting only few hours[7]
We report that bears display a plasma lipid profile, i.e., increased plasma levels of non-esterified fatty acids (NEFAs) and TAG (Fig. 1), typical of a phase 2 fast with lipolysis providing the main source of energy during winter
Summary
To investigate mechanisms by which hibernators avoid atherogenic hyperlipidemia during hibernation, we assessed lipoprotein and cholesterol metabolisms of free-ranging Scandinavian brown bears (Ursus arctos). Denning American black bears (Ursus americanus) showed a significant doubling of NEFA levels in all classes (saturates, monemes and polyenes), along with a 33% increase in albumin, i.e., the plasma fatty acid binding protein, leading to higher NEFA/albumin ratios (4:1) compared to those (3:1) of active black bears in summer[21]. Despite such seasonal hyperlipidemia and hypercholesterolemia, hibernators do not spontaneously develop pathophysiological syndromes, such as atherosclerosis or other complications linked to lipid peroxidation and oxidative damages during h ibernation[22]. Oxysterols, which are oxidized derivatives of cholesterol, and isoprostanes, such as prostaglandin F2 isomers, are known for their pro-inflammatory and pro-oxidative properties and these molecules play key roles in the process of atherogenic d yslipidemia[43,44] (for reviews s ee[45,46])
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