Body Protein Sparing in Hibernators: A Source for Biomedical Innovation

Abstract

Proteins are not only the major structural components of living cells but also ensure essential physiological functions within the organism. Any change in protein abundance and/or structure is at risk for the proper body functioning and/or survival of organisms. Death following starvation is attributed to a loss of about half of total body proteins, and body protein loss induced by muscle disuse is responsible for major metabolic disorders in immobilized patients, and sedentary or elderly people. Basic knowledge of the molecular and cellular mechanisms that control proteostasis is continuously growing. Yet, finding and developing efficient treatments to limit body/muscle protein loss in humans remain a medical challenge, physical exercise and nutritional programs managing to only partially compensate for it. This is notably a major challenge for the treatment of obesity, where therapies should promote fat loss while preserving body proteins. In this context, hibernating species preserve their lean body mass, including muscles, despite total physical inactivity and low energy consumption during torpor, a state of drastic reduction in metabolic rate associated with a more or less pronounced hypothermia. The present review introduces metabolic, physiological, and behavioral adaptations, e.g., energetics, body temperature, and nutrition, of the torpor or hibernation phenotype from small to large mammals. Hibernating strategies could be linked to allometry aspects, the need for periodic rewarming from torpor, and/or the ability of animals to fast for more or less time, thus determining the capacity of individuals to save proteins. Both fat- and food-storing hibernators rely mostly on their body fat reserves during the torpid state, while minimizing body protein utilization. A number of them may also replenish lost proteins during arousals by consuming food. The review takes stock of the physiological, molecular, and cellular mechanisms that promote body protein and muscle sparing during the inactive state of hibernation. Finally, the review outlines how the detailed understanding of these mechanisms at play in various hibernators is expected to provide innovative solutions to fight human muscle atrophy, to better help the management of obese patients, or to improve the ex vivo preservation of organs.

Hibernating brown bears are protected against atherogenic dyslipidemia

“…1 ), typical of a phase 2 fast with lipolysis providing the main source of energy during winter. Such an increase in lipid mobilization reflects the occurrence of a switch in substrate metabolism toward the sparing of muscle proteins during hibernation (for review, see 68 ). Our results further highlight that hibernating bears handle fluxes of TAGs and CHT via futile cycles and re-esterification through lipoprotein metabolism.…”

“…In particular, diet is seasonally variable in bears in Scandinavia, as elsewhere 104 , 105 . In autumn, brown bears in Scandinavia build up fat reserves by mainly feeding on berries, such as from the Vaccinum family, that contribute most (49–81%) of the dietary energy content of the bears 103 – 105 , and also provide them with a major source of antioxidant molecules that directly impact on their hibernation physiology and performances, notably in regard to lipid metabolism and protein/muscle maintenance during hibernation (for review, see 68 ).…”

Molecular liver fingerprint reflects the seasonal physiology of the grey mouse lemur (Microcebus murinus) during winter

“…A possible hypothesis is that the rate of flux of amino acids toward the liver, a key regulator of ureagenesis, may likely be low in LW due to a decrease in the muscle efflux of amino acids. This idea is supported by the self-imposed 'caloric restriction' situation (according to the fact that food intake spontaneously decreases) in LW, which seems to resemble the low energy diets in several animals, including food-storing hibernators, which maintain their protein pool and limit muscle loss [10]. Hence, the reduction in food intake, together with increased energy expenditure (see below), is accompanied with the mobilization of fat stores in LW lemurs, which might help spare body proteins.…”

Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction

“…Thus, the hibernation phenomenon is more than biologically interesting because understanding how organs cope with the stresses of hibernation could have direct clinical relevance (30) and especially for cardiovascular disease, such as myocardial infarction. Although we cannot rule out the possible role of parasympathetic and sympathetic nervous systems in the regulation of the cardiac function in bears entering or coming out of hibernation (3,8), it is likely that circulating compounds may contribute to cardioprotection in vivo.…”