liver-cold-storage-transplantation-cold-adaptive-daurian-ground

Liver Cold Storage and Transplantation in the Cold-Adaptive Daurian Ground Squirrels

In liver transplantation, the functional recovery of donor grafts following extended cold storage is a major challenge. The same obstacle applies to ...

post-liver-transplantation-management-specimen-collection-daurian

Post-Liver Transplantation Management and Specimen Collection in Daurian Ground Squirrels for Single-Cell RNA Sequencing

Graft functional recovery and graft-host immunocompatibility represent major prognostic concerns following liver transplantation. Critically, conventional ...

The Daurian ground squirrel (Spermophilus dauricus) accumulates large amounts of body fat during pre-hibernation fattening. Leptin, an adipose-derived hormone, plays important roles in energy balance and thermogenesis. We predicted that body fat accumulation would lead to the elevation of leptin concentration while its effect on satiety would be suppressed in hypothalamus during fattening. In addition, the uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) would increase and correlated positively with leptin concentration before hibernation. Here, we measured serum leptin concentration and leptin mRNA in white adipose tissue (WAT), hypothalamic neuropeptides involved in energy regulation and UCP1 in BAT before, during and after fattening in squirrels. The fat mass gradually increased during fattening but serum leptin increased mainly in the late phase of fattening, which was consistent with leptin mRNA expression in WAT. During fattening, the mRNA of hypothalamic leptin receptor was up-regulated and correlated positively with serum leptin. Orexigenic neuropeptide Y mRNA increased by 67%; however agouti-related peptide remained unchanged before hibernation. There was no significant change in anorexigenic neuropeptide mRNA. No change in suppressor of cytokine signaling-3 and protein tyrosine phosphatase-1B was detected. UCP1 mRNA expression and protein content in BAT increased significantly after fattening. These changes were independent of environmental conditions and serum leptin concentration. Our results suggest that the dissociation of leptin production and adiposity during fattening may facilitate fat accumulation. No evidence of suppressed leptin signal was found in fattening squirrels. The UCP1 recruitment in post-fattening squirrels could occur without winter-like acclimation and increased leptin.

The expression of leptin, hypothalamic neuropeptides and UCP1 before, during and after fattening in the Daurian ground squirrel (Spermophilus dauricus).

Body fat storage before hibernation affects the timing of immergence in Daurian ground squirrels (Spermophilus dauricus). Leptin is an adipose signal and plays vital role in energy homeostasis mainly by action in brain. To test the hypothesis that leptin plays a role in facilitating the process of hibernation, squirrels were administrated with recombinant murine leptin (1μg/day) through intracerebroventricular (ICV) injection for 12 days during fattening. From day 7 to 12, animals were moved into a cold room (5±1°C) with constant darkness which functioned as hibernaculum. Energy intake, body mass and core body temperature (Tb) were continuously monitored throughout the course of experiment. Resting metabolic rate (RMR) was measured under both warm and cold conditions. At the end of leptin administration, we measured the serum concentration of hormones related to energy regulation, mRNA expression of hypothalamic neuropeptides and uncoupling protein 1 (UCP1) levels in brown adipose tissue (BAT). Our results showed that during leptin administration, the cumulative food intake and increase of body mass were suppressed while Tb and RMR were unaltered. The proportion of torpid squirrels was not different between two groups. At the end of leptin administration, the expressions of hypothalamic neuropeptide Y and agouti gene-related protein were suppressed. There were no differences in UCP1 mRNA expression or protein content in BAT between groups. Our data suggest that leptin can affect energy intake via hypothalamic neuropeptides, but is not involved in the initiation of hibernation in fattening Daurian ground squirrels.

Leptin regulates energy intake but fails to facilitate hibernation in fattening Daurian ground squirrels (Spermophilus dauricus).

Energy balance and thermoregulation in many fat-storing seasonal hibernators show a circannual rhythm. To understand the physiological mechanisms of the seasonal pre-hibernation fattening related to the regulation of energy expenditure and thermogenesis, we cold-exposed fattening Daurian ground squirrels (Spermophilus dauricus) in late summer for 3 weeks. We predicted that cold-exposed squirrels would increase food intake rather than express torpor to accommodate both fattening and thermoregulatory fuel allocation. Food intake and body mass were quantified. After 3 weeks, body compositions, serum leptin concentration, expression of hypothalamic neuropeptides related to regulation of energy balance and uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) were measured. There was no change in body mass after 3-weeks of cold exposure. Hypothalamic orexigenic neuropeptides and UCP1 levels in BAT were up-regulated after cold exposure. Food intake, serum leptin concentration and the expression of leptin signal suppressors, suppressor of cytokine signaling 3 and protein tyrosine phosphatase 1B, in hypothalamus showed no differences compared with controls. The core body temperature was unaffected by cold exposure. Our data suggest that cold exposure affected fattening mainly because of the increased heat loss, whereas energy balance and thermoregulation are under control of a strong circannual rhythm in the Daurian ground squirrels.

Cold exposure increased hypothalamic orexigenic neuropeptides but not food intake in fattening Daurian ground squirrels.

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.

Transcriptional regulation of intermolecular Ca signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis.

Torpor, an adaptive hypometabolic state in response to fasting, is characterized by pronounced reductions in body temperature, heart rate, and thermogenesis. However, how the brain orchestrates these physiological changes to induce torpor and the relationships among them remain elusive. Inhibiting catecholaminergic (CA) neurons in the ventrolateral medulla (VLM) significantly impairs torpor in mice, while their activation reduces body temperature, heart rate, energy expenditure, physical activity, and thermogenesis. Importantly, the heart rate decline precedes body temperature reduction, resembling patterns observed in natural torpid animals. Moreover, a likely causal relationship exists between heart rate reduction and body temperature decline. VLM-CA neurons may regulate heart rate and thermogenesis through projections to the dorsal motor vagal nucleus and medial preoptic area, respectively. Additionally, these neurons are conserved in Daurian ground squirrels and become active before hibernation, indicating their potential role in hibernation. Here, we find that VLM-CA neurons play important roles in fasting-induced torpor.

ArticleTotal : 2	Year
Publication title	2025
Publication title	2025

Article	Year
The expression of leptin, hypothalamic neuropeptides and UCP1 before, during and after fattening in the Daurian ground squirrel (Spermophilus dauricus). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology\| PubMed ID: 25711781	2015
Leptin regulates energy intake but fails to facilitate hibernation in fattening Daurian ground squirrels (Spermophilus dauricus). Journal of thermal biology\| PubMed ID: 27033037	2016
Cold exposure increased hypothalamic orexigenic neuropeptides but not food intake in fattening Daurian ground squirrels. Zoology (Jena, Germany)\| PubMed ID: 32947220	2020
Transcriptional regulation of intermolecular Ca signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 33785600	2021
Brainstem catecholaminergic neurons induce torpor during fasting by orchestrating cardiovascular and thermoregulation changes. Nature communications\| PubMed ID: 40593766	2025

Xin Xing

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