06.10.2021: Brown bears build up large fat reserves as a source of energy to fuel their hibernation. Despite the total physical inactivity, however, hibernating bears do not develop any cardiovascular disease during several months in winter. An international study led by Vetmeduni that was recently published in Scientific Reports shows that brown bears have effective protective mechanisms during hibernation to prevent damage to their blood plasma and muscles despite profound changes in their lipid metabolism and elevated lipid levels.

Mammalian hibernation allows animals to survive harsh environmental conditions, including food shortages, during winter. Hibernators accumulate large fat reserves and nearly double their body mass from spring to early fall, with a fat accumulation leading to a state that would be considered obese in humans. Hibernating species then enter a state of depressed metabolism, known as torpor, which leads to a substantial reduction of energy needs and enables the animals to survive the winter.

Hibernating brown bears protected against atherogenic metabolic disorders

To investigate the mechanisms by which hibernators avoid the metabolic disorder known as atherogenic dyslipidemia during hibernation, the researchers assessed lipoprotein and cholesterol metabolisms of free‑ranging Scandinavian brown bears (Ursus arctos) by measuring lipoprotein sizes, subclasses and composition, triglyceride‑related plasma‑enzyme activities, and muscle lipid composition along with plasma‑levels of antioxidant capacities and inflammatory markers in bears during winter and summer. Their findings: “Although nearly all lipid levels were higher in the winter, a nearly one-third increase in activity of cholesteryl ester transfer protein, a key enzyme involved in cholesterol recycling based on futile cycles of re-esterification via lipoprotein metabolism, helped to stabilize the lipid composition of high‑density lipoproteins (HDL). The concentration of inflammatory metabolites declined in winter and correlated inversely with cardioprotective HDL2b‑proportions and HDL sizes that increased during hibernation,” says first author Sylvain Giroud, a wildlife and physiological ecologist at the Research Institute of Wildlife Ecology at Vetmeduni.

Obese but healthy hibernators

According to Giroud, lower muscle cholesterol levels and reduced lecithin‑cholesterol acyltransferase activity in winter suggest that hibernation involves a tightly controlled peripheral cholesterol synthesis and/or release. Moreover, the greater plasma antioxidant capacities prevent excessive lipid‑specific oxidative damages in plasma and possibly in muscles. This mechanism helps brown bears to manage large lipid fluxes during hibernation without developing adverse atherogenic effects of the sort associated with obesity in humans and non‑hibernators.

New insights in the fight against atherosclerosis

The new insights gained from this study are especially interesting as atherogenic dyslipidemia particularly affects humans and some domestic animals. The metabolic disorder is characterized by the accumulation of cholesteryl esters and other lipids on the inner walls of arterial blood vessels, which leads to atherosclerosis and subsequently damages the coronary arteries, carotid arteries and the large arteries of the legs. The understanding gained from the study of brown bears is therefore also of great interest for developing new strategies against atherosclerosis in humans.

The article “Hibernating brown bears are protected against atherogenic dyslipidemia” by Sylvain Giroud, Isabelle Chery, Mathilde Arrivé, Michel Prost, Julie Zumsteg, Dimitri Heintz, Alina L. Evans, Guillemette Gauquelin‑Koch, Jon M. Arnemo, Jon E. Swenson, Etienne Lefai, Fabrice Bertile, Chantal Simon and Stéphane Blanc was published in Scientific Reports.