Anabolic Transcriptional Changes and Muscle Atrophy, Bone Loss Prevention in Hibernating Black Bears

Physical inactivity reduces mechanical load on the skeleton, which leads to muscle atrophy and loss of bone mass in non hibernating mammalian species. Although bears are largely inactive during hibernation, they show no loss in bone mass and less loss in muscle mass and strength than would be anticipated over such a prolonged period of inactivity.  To obtain insight into molecular mechanisms preventing disuse bone and muscle loss, we conducted a large-scale screening of transcriptional changes comparing winter hibernating and summer non hibernating black bears using a custom 12,800 probe cDNA microarray. The pathway analysis showed significant enrichment of the protein biosynthesis category by over-expressed genes in both liver and skeletal muscle during hibernation. Coordinated reduction in transcription of genes involved in the urea cycle and amino acid catabolism in liver suggests redirection of amino acids from catabolic pathways to protein biosynthesis. These findings imply induction of translation that may reduce muscle atrophy during hibernation.  In bone of hibernating bears we detected elevated proportion of over-expressed genes in six functional sets related to tissue development including skeletal development and bone biosynthesis. Coordinated induction in transcription of genes involved in anabolic processes implies elevation of anabolic activity in bone that may compensate for reduction in bone formation induced by disuse and prevent bone loss. Elevated expression of multiply anabolic genes without induction of genes involved in catabolism suggests similar adaptive mechanisms that contribute to the preservation of bone and muscle mass over periods of physical inactivity and starvation during hibernation.