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Although the Djungarian hamster ( Phodopus sungorus ) is a seasonality model, it presents substantial variability in winter acclimation. In response to short photoperiod, some individuals express a suite of winter traits such as low body mass, regressed gonads, white fur, and daily torpor, while others develop only some adjustments or maintain a summer phenotype. Despite comprehensive research, the mechanisms underlying polymorphism of winter phenotype are still unknown. We compared key elements of the hypothalamic thyroid hormone system, as well as the tanycyte architecture in hamsters of both sexes. Individuals presented different responses to short photoperiod characterized either as phenotypes (non-responder, partial-responder and full-responder) or photoresponsive index. We measured the expression of genes coding iodothyronine deiodinase 2 and 3, monocarboxylate transporter 8, thyrotropin-releasing hormone, and somatostatin in 40 individuals and counted the number of immunolabeled tanycyte processes in standardized regions of interest around the third ventricle in 30 individuals. Animals acclimated to short photoperiod presented a downregulation of diodinase 2 and somatostatin and an upregulation of deiodinase 3, as well as a decreased number of tanycyte processes, compared to long photoperiod-exposed individuals. Although phenotypes did not differ in gene expression, the higher the photoresponsive index, the lower was the deiodinase 2 expression and the higher the deiodinase 3 expression. Partial-responders and full-responders had less tanycyte processes than non-responders, and the number of tanycyte processes correlated with the photoresponsive index. Sexes differed neither in their seasonal response, nor hypothalamic gene expression, but females had more tanycyte processes. Our results are in accordance with studies emphasizing the pivotal role of thyroid hormones in seasonal response. We suggest that the whole spectrum of winter phenotypes exists within the population of Djungarian hamsters and that it is reflected also at the level of neuroendocrine regulation. However, the neuroendocrine underpinnings of winter phenotype polymorphism require further investigation.

Prevalence of obesity among infants and children below 5 years of age is rising dramatically, and early childhood obesity is a forerunner of obesity and obesity-associated diseases in adulthood. Childhood obesity is hence one of the most serious public health challenges today. Here, we have identified a mother-to-child lipid signaling that protects from obesity. We have found that breast milk-specific lipid species, so-called alkylglycerol-type (AKG-type) ether lipids, which are absent from infant formula and adult-type diets, maintain beige adipose tissue (BeAT) in the infant and impede the transformation of BeAT into lipid-storing white adipose tissue (WAT). Breast milk AKGs are metabolized by adipose tissue macrophages (ATMs) to platelet-activating factor (PAF), which ultimately activates IL-6/STAT3 signaling in adipocytes and triggers BeAT development in the infant. Accordingly, lack of AKG intake in infancy leads to a premature loss of BeAT and increases fat accumulation. AKG signaling is specific for infants and is inactivated in adulthood. However, in obese adipose tissue, ATMs regain their ability to metabolize AKGs, which reduces obesity. In summary, AKGs are specific lipid signals of breast milk that are essential for healthy adipose tissue development.

Djungarian hamsters are small rodents that show pronounced physiological acclimations in response to changes in photoperiod, and unfavorable environmental conditions such as reduced food availability and low external temperature. These include substantial adjustments, such as severe body weight loss and the use of daily torpor. Torpor is a state of decreased physiological activity in eutherms, usually marked by low metabolic rate and a reduced body temperature. In this study, we investigated the effects of photoperiodic acclimation and food deprivation on systemic iron metabolism in Djungarian hamsters. Our study illustrates the association between liver iron levels and the incidence of torpor expression during the course of the experiment. Moreover, we show that both, acclimation to short photoperiods and long-term food restriction, associated with iron sequestration in the liver. This effect was accompanied with hypoferremia and mild reduction in the expression of principal iron-hormone, hepcidin. In addition to iron, the levels of manganese, selenium, and zinc were increased in the liver of hamsters under food restriction. These findings may be important factors for regulating physiological processes in hamsters, since iron and other trace elements are essential for many metabolic and physiological processes.

The energy‐saving strategy of Djungarian hamsters (Phodopus sungorus, Cricetidae) to overcome harsh environmental conditions comprises of behavioral, morphological, and physiological adjustments, including spontaneous daily torpor, a metabolic downstate. These acclimatizations are triggered by short photoperiod and orchestrated by the hypothalamus. Key mechanisms of long‐term photoperiodic acclimatizations have partly been described, but specific mechanisms that acutely control torpor remain incomplete. Here, we performed comparative transcriptome analysis on hypothalamus of normometabolic hamsters in their summer‐ and winter‐like state to enable us to identify changes in gene expression during photoperiodic acclimations. Comparing nontorpid and torpid hamsters may also be able to pin down mechanisms relevant for torpor control. A de novo assembled transcriptome of the hypothalamus was generated from hamsters acclimated to long photoperiod or to short photoperiod. The hamsters were sampled either during long photoperiod normothermia, short photoperiod normothermia, or short photoperiod‐induced spontaneous torpor with a body temperature of 24.6 ± 1.0 °C, or. The mRNA‐seq analysis revealed that 32 and 759 genes were differentially expressed during photoperiod or torpor, respectively. Biological processes were not enriched during photoperiodic acclimatization but were during torpor, where transcriptional and metabolic processes were reinforced. Most extremely regulated genes (those genes with |log2(FC)| > 2.0 and padj < 0.05 of a pairwise group comparison) underpinned the role of known key players in photoperiodic comparison, but these genes exhibit adaptive and protective adjustments during torpor. Targeted analyses of genes from potentially involved hypothalamic systems identified gene regulation of previously described torpor‐relevant systems and a potential involvement of glucose transport. Djungarian hamsters (Phodopus sungorus) use morphological and physiological changes to overcome extreme environmental conditions. These acclimatizations include spontaneous daily torpor. To uncover the mechanisms behind torpor, samples were collected from nontorpid and torpid hamsters during summer‐ or winter‐like photoperiod. The pipeline comprised a de novo transcriptome assembly, a mapping against Mus musculus, and several analyses to identify the most relevant data. Analysis of the hypothalamus transcriptome confirms known and suggests new mechanisms that might orchestrate seasonal acclimation and metabolic downstates in photoperiodic rodents.

The Djungarian hamster is a rodent species that expresses both spontaneous daily torpor (SDT) when acclimated to winter conditions as well as fasting-induced torpor (FIT) during summer. In an earlier report we argued that these two thermoregulatory phenomena differ in several parameters. In the present study, we further complete this comparison by showing that metabolic rate patterns differ between both SDT and FIT. SDT bouts were significantly longer and deeper compared to FIT bouts. Additionally, respiratory quotient measures support the view that SDT is entered from a state of energetic balance while FIT appears to be an emergency shutdown of energy demanding thermogenesis due to a shortage of energy sources. In a second experiment, we also confirm that brief periods of food restriction during the hamsters’ torpor season increase the frequency of SDT, but do not affect its depth or duration. Although winter-acclimated animals could flexibly alter torpor frequency in order to stay in energetic balance, we also found evidence for torpor expression patterns that resembled FIT, rather than SDT. Consequently, if energetic challenges cannot be compensated with increased SDT expression any longer, the hamsters seem to be driven in a negative energy balance resulting in FIT as a last resort.

The Djungarian hamster (Phodopus sungorus) is a prominent model organism for seasonal acclimatization, showing drastic whole-body physiological adjustments to an energetically challenging environment, which are considered to also involve the gut microbiome. Fecal samples of hamsters in long photoperiod and again after twelve weeks in short photoperiod were analyzed by 16S-rRNA sequencing to evaluate seasonal changes in the respective gut microbiomes. In both photoperiods, the overall composition was stable in the major superordinate phyla of the microbiota, with distinct and delicate changes of abundance in phyla representing each <1% of all. Elusimicrobia, Tenericutes, and Verrucomicrobia were exclusively present in short photoperiod hamsters. In contrast to Elusimicrobium and Aneroplasma as representatives of Elusimicrobia and Tenericutes, Akkermansia muciniphila is a prominent gut microbiome inhabitant well described as important in the health context of animals and humans, including neurodegenerative diseases and obesity. Since diet was not changed, Akkermansia enrichment appears to be a direct consequence of short photoperiod acclimation. Future research will investigate whether the Djungarian hamster intestinal microbiome is responsible for or responsive to seasonal acclimation, focusing on probiotic supplementation.

The Djungarian hamster (Phodopus sungorus) is a prominent model organism for seasonal acclimatization, showing drastic whole-body physiological adjustments to an energetically challenging environment, which are considered to also involve the gut microbiome. Fecal samples of hamsters in long photoperiod and again after twelve weeks in short photoperiod were analyzed by 16S-rRNA sequencing to evaluate seasonal changes in the respective gut microbiomes. In both photoperiods, the overall composition was stable in the major superordinate phyla of the microbiota, with distinct and delicate changes of abundance in phyla representing each <1% of all. Elusimicrobia, Tenericutes, and Verrucomicrobia were exclusively present in short photoperiod hamsters. In contrast to Elusimicrobium and Aneroplasma as representatives of Elusimicrobia and Tenericutes, Akkermansia muciniphila is a prominent gut microbiome inhabitant well described as important in the health context of animals and humans, including neurodegenerative diseases and obesity. Since diet was not changed, Akkermansia enrichment appears to be a direct consequence of short photoperiod acclimation. Future research will investigate whether the Djungarian hamster intestinal microbiome is responsible for or responsive to seasonal acclimation, focusing on probiotic supplementation.

In nature Siberian hamsters utilize the decrement in day length following the summer solstice to implement physiological adaptations in anticipation of the forthcoming winter, but also exploit an intrinsic interval timer to initiate physiological recrudescence following the winter solstice. However, information is lacking on the temporal dynamics in natural photoperiod of photoperiodically regulated genes and their relationship to physiological adaptations. To address this, male Siberian hamsters born and maintained outdoors were sampled every month over the course of one year. As key elements of the response to photoperiod, thyroid hormone signalling components were assessed in the hypothalamus. From maximum around the summer solstice (late-June), Dio2 expression rapidly declined in advance of physiological adaptations. This was followed by a rapid increase in Mct8 expression (T3/T4 transport), peaking early-September before gradually declining to minimum expression by the following June. Di o3 showed a transient peak of expression beginning late-August. A recrudescence of testes and body mass occurred from mid-February, but Dio2 expression remained low until late-April of the following year, converging with the time of year when responsiveness to short-day length is re-established. Other photoperiodically regulated genes show temporal regulation, but of note is a transient peak in Gpr 50 around late-July.

Hibernation enables many species of the mammalian kingdom to overcome periods of harsh environmental conditions. During this physically inactive state metabolic rate and body temperature are drastically downregulated, thereby reducing energy requirements (torpor) also over shorter time periods. Since blood cells reflect the organism´s current condition, it was suggested that transcriptomic alterations in blood cells mirror the torpor-associated physiological state. Transcriptomics on blood cells of torpid and non-torpid Djungarian hamsters and QIAGEN Ingenuity Pathway Analysis (IPA) revealed key target molecules (TMIPA), which were subjected to a comparative literature analysis on transcriptomic alterations during torpor/hibernation in other mammals. Gene expression similarities were identified in 148 TMIPA during torpor nadir among various organs and phylogenetically different mammalian species. Based on TMIPA, IPA network analyses corresponded with described inhibitions of basic cellular mechanisms and immune system-associated processes in torpid mammals. Moreover, protection against damage to the heart, kidney, and liver was deduced from this gene expression pattern in blood cells. This study shows that blood cell transcriptomics can reflect the general physiological state during torpor nadir. Furthermore, the understanding of molecular processes for torpor initiation and organ preservation may have beneficial implications for humans in extremely challenging environments, such as in medical intensive care units and in space.

Childhood obesity is a serious public health crisis and a critical factor that determines future obesity prevalence. Signals affecting adipocyte development in early postnatal life have a strong potential to trigger childhood obesity; however, these signals are still poorly understood. We show here that mitochondrial (mt)RNA efflux stimulates transcription of nuclear-encoded genes for mitobiogenesis and thermogenesis in adipocytes of young mice and human infants. While cytosolic mtRNA is a potential trigger of the interferon (IFN) response, young adipocytes lack such a response to cytosolic mtRNA due to the suppression of IFN regulatory factor (IRF)7 expression by vitamin D receptor signalling. Adult and obese adipocytes, however, strongly express IRF7 and mount an IFN response to cytosolic mtRNA. In turn, suppressing IRF7 expression in adult adipocytes restores mtRNA-induced mitobiogenesis and thermogenesis and eventually mitigates obesity. Retrograde mitochondrion-to-nucleus signalling by mtRNA is thus a mechanism to evoke thermogenic potential during early adipocyte development and to protect against obesity. Hoang et al. show that mitochondrial RNA in young beige adipocytes triggers mitobiogenesis and thermogenesis, while an interferon response is avoided through vitamin D-mediated suppression of IRF7 expression.