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“Background Autophagy Compound Library hibernation is a strategy employed by many different mammals presumably as a means for energy conservation during periods of great thermal stress and limited food resources

[1, 2]. Ground squirrels of the genus Spermophilus are exemplary hibernators. Their winter seasons are characterized by bouts of torpor wherein body temperature may approach ambient to as low as -2°C [3, 4] and metabolic rates may be as low as 1% of the active rate [5]. These torpor bouts may last 1–3 weeks and are interrupted by brief (~20–24 h) sojourns to body temperatures and metabolic rates typical of an active animal. During the winter, golden-mantled ground squirrels (S. lateralis) are anorexic. Even when housed with free access PCI-34051 supplier to food, very few of these animals will eat for the entire ~6 month hibernation season (personal observations). Instead, animals rely on immense fat stores that were gained in an anticipatory period during late summer [2]. Hibernating animals utilize a primarily fat-based metabolism as reflected by a typical respiratory quotient (RQ) of 0.71

but employ a more carbohydrate-based metabolism (RQ = ~0.9) during the interbout-arousal [6]. As expected, the consequences of the anorexic period include a profound disuse atrophy of the gut and the physiology of this atrophy has been well described [7–9]. Although a large number of studies have used the liver as a model organ for examining the effects of hibernation on various metabolic activities such as protein synthesis, we are unaware of any studies

that have examined digestive hepatobiliary function per se during hibernation. One might expect dramatic changes in liver function Protein Tyrosine Kinase inhibitor due to the extended anorexia, metabolic fuel privation, and severe physiological conditions inherent to hibernation. Mortality rates during hibernation are high; as many as 40–70% of squirrels fail to emerge from the burrow the following spring Branched chain aminotransferase [10]. Although no data are available as to the cause of this mortality, likely explanations include a metabolic disorder or a lack of energetic supplies to withstand the extended anorexia. In maintaining laboratory colonies for other experiments, we occasionally encounter some animals that fail to hibernate (< 5% of all animals; personal observations). These animals typically lose weight quickly and die during the winter. We observed a marked difference in bile color of these animals. As a result of this observation and to characterize hepatic function during hibernation, we examined the constituents of bile in active and hibernating squirrels. Results In our experience, golden-mantled ground squirrels have proven to be very reliable hibernators in the laboratory. Indeed, we have observed hibernation at ambient temperatures of 20°C, with a variety of lighting conditions, and in the presence of free access to food. Rarely, some animals fail to hibernate (< 5% of all animals; personal observations).