Endocrine Regulation of Bone and Energy Metabolism in Hibernating Mammals

Abstract

Precise coordination among organs is required to maintain homeostasis throughout hibernation. This is particularly true in balancing bone remodeling processes (bone formation and resorption) in hibernators experiencing nutritional deprivation and extreme physical inactivity, two factors normally leading to pronounced bone loss in non-hibernating mammals. In recent years, important relationships between bone, fat, reproductive, and brain tissues have come to light. These systems share interconnected regulatory mechanisms of energy metabolism that potentially protect the skeleton during hibernation. This review focuses on the endocrine and neuroendocrine regulation of bone/fat/energy metabolism in hibernators. Hibernators appear to have unique mechanisms that protect musculoskeletal tissues while catabolizing their abundant stores of fat. Furthermore, the bone remodeling processes that normally cause disuse-induced bone loss in non-hibernators are compared to bone remodeling processes in hibernators, and possible adaptations of the bone signaling pathways that protect the skeleton during hibernation are discussed. Understanding the biological mechanisms that allow hibernators to survive the prolonged disuse and fasting associated with extreme environmental challenges will provide critical information regarding the limit of convergence in mammalian systems and of skeletal plasticity, and may contribute valuable insight into the etiology and treatment of human diseases.

Metabolic Flexibility: Hibernation, Torpor, and Estivation

“…In grizzly bears, this maintenance is achieved despite a decrease in bone turnover (191), presumably by balanced reductions in the activities of both osteoblasts and osteoclasts. From a recent review (80), however, it is evident that the regulation of this balance in hibernation is complex and not yet fully understood.…”

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

“…Thus, leptin could contribute to the control of balanced bone remodelling during hibernation and aestivation. In hibernators, serum leptin usually peaks during the autumn as a result of increased food intake in preparation for dormancy (Doherty et al, 2014). Elevated concentrations of leptin during pre-hibernation and early hibernation have been documented in species such as bears, woodchucks, marmots and ground squirrels (see Doherty et al, 2014, and references therein), before the level of leptin gradually drops well into the hibernation season.…”

“…In hibernators, serum leptin usually peaks during the autumn as a result of increased food intake in preparation for dormancy (Doherty et al, 2014). Elevated concentrations of leptin during pre-hibernation and early hibernation have been documented in species such as bears, woodchucks, marmots and ground squirrels (see Doherty et al, 2014, and references therein), before the level of leptin gradually drops well into the hibernation season. It has been suggested that suppressed bone resorption in hibernating black bears may be due to leptin-mediated stimulation of hypothalamic CART (Seger et al, 2011).…”

Exploring the Bone Proteome to Help Explain Altered Bone Remodeling and Preservation of Bone Architecture and Strength in Hibernating Marmots

“…The marmots were synchronized in January so they would all be on the same torpor bout schedule, and necropsy could be scheduled for midtorpor as opposed to during interbout arousal, when metabolism increases for short durations. The stage of hibernation may contribute to variations in the physiology of bone remodeling processes (Doherty et al 2014). It is possible that one or more of the marmots were out of sync and were entering or exiting a torpor bout (i.e., at a higher metabolic state) at the time of sample collection, and this may explain some of the outlying values we found.…”