Hypothalamic control systems show differential gene expression during spontaneous daily torpor and fasting-induced torpor in the Djungarian hamster (Phodopus sungorus)

Abstract

Djungarian hamsters are able to use spontaneous daily torpor (SDT) during the winter season as well as fasting-induced torpor (FIT) at any time of the year to cope with energetically challenging environmental conditions. Torpor is a state of severely reduced metabolism with a pronounced decrease in body temperature, which enables animals to decrease their individual energy requirements. Despite sharing common characteristics, such as reduced body mass before first torpor expression and depressed metabolism and body temperature during the torpid state, FIT and SDT differ in several physiological properties including torpor bout duration, minimal body temperature, fuel utilization and circadian organization. It remains unclear, whether SDT and FIT reflect the same phenomenon or two different physiological states. The hypothalamus has been suggested to play a key role in regulating energy balance and torpor. To uncover differences in molecular control mechanisms of torpor expression, we set out to investigate hypothalamic gene expression profiles of genes related to orexigenic (Agrp/Npy), circadian clock (Bmal1/Per1) and thyroid hormone (Dio2/Mct8) systems of animals undergoing SDT and FIT during different torpor stages. Orexigenic genes were mainly regulated during FIT and remained largely unaffected by SDT. Expression patterns of clock genes showed disturbed circadian clock rhythmicity in animals undergoing FIT, but not in animals undergoing SDT. During both, SDT and FIT, decreased Dio2 expression was detected, indicating reduced hypothalamic T3 availability in both types of torpor. Taken together, our results provide evidence that SDT and FIT also differ in certain central control mechanisms and support the observation that animals undergoing SDT are in energetical balance, whereas animals undergoing FIT display a negative energy balance. This should be carefully taken into account when interpreting data in torpor research, especially from animal models of fasting-induced hypometabolism such as mice.

Gonadal hormones influence core body temperature during calorie restriction

“…The next 20 h of the day present a period of fasting until food is provided again the next day. Thus, the hypothermic response occurs due to this fasting period and the presumed circadian dysregulation of molecules modulating daily energy expenditure in the face of reduced calorie intake [22]. If the food would have been provided during the inactive phase of the day, most likely the animals would have experienced the hypothermic response during the active phase of the day.…”

Gene expression profiling during hibernation in the European hamster

“…During torpor, minimal functional brain activity persists to prevent nervous tissue damage and to allow the animals to rapidly and completely recover from hypothermia. Recent studies involving RNASeq analyses of the hypothalamus and cerebral cortex from thirteen-lined ground squirrels (true hibernator) 43 , and of the hypothalamus from Djungarian hamsters (daily torpidators) 48 , at various stages of torpor or interbouts have reported different strategies implemented in the hypothalamus and cerebral cortex during hibernation. In the hypothalamus, the differentially expressed genes are involved in protection against DNA damage, protein turnover through ubiquitination, feeding and satiety signalling, seasonal timing mechanisms, and fuel utilization.…”

“…This approach implies that hibernators have no specific set of genes dedicated to hibernation, but rather rely on differential expression of genes that exist in most mammals 47 . Such gene profiling could be performed using an unbiased wide transcriptomic analysis, such RNASeq 43 , 45 , 48 , or a candidate genes approach 49 . In our present study, we aimed to establish a molecular signature of hibernation by analysing the expression of genes with potential involvement in energy homeostasis, torpor regulation, and daily or seasonal timing, in eight central and peripheral organs sampled during three different hibernation phases in the European hamster.…”

What can seasonal models teach us about energy balance?

“…Over seasons, only subtle gene expression changes could be found in these signaling pathways, suggesting appropriate energy balance despite the pronounced differences in body weight. Also during spontaneous daily torpor no gene expression changes were found (Cubuk et al 2017a). Although no signaling pathways could be nailed down yet, it has been shown that lesions of the arcuate nucleus prevented torpor in short photoperiod-adapted Djungarian hamsters, clearly showing its participation (Pelz et al 2008).…”

“…However, gene expression data of the T3-activating enzyme Type 2 deiodinase support this idea. The downregulation of this enzyme in the hypothalamus during spontaneous daily and fasting-induced torpor suggests an important role of reduction of T3 availability in natural situations (Bank et al 2015, Cubuk et al 2017a. However, many other components like deiodinase enzymes, transporters and receptors are involved in T3 availability in the brain and require much more detailed analysis over the course of a torpor bout (Fig.…”