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Ambient temperatures have great impacts on thermoregulation of small mammals. Brown adipose tissue (BAT), an obligative thermogenic tissue for small mammals, is localized not only in the interscapular depot (iBAT), but also in supraclavicular, infra/subscapular, cervical, paravertebral, and periaortic depots. The iBAT is known for its cold-induced thermogenesis, however, less has been paid attention to the function of BAT at other sites. Here, we investigated the function of BAT at different sites of the body during cold acclimation in a small rodent species. As expected, Brandt's voles (Lasiopodomys brandtii) consumed more food and reduced the body mass gain when they were exposed to cold. The voles increased resting metabolic rate and maintained a relatively lower body temperature in the cold (36.5 ± 0.27 °C) compared to those in the warm condition (37.1 ± 0.36 °C). During cold acclimation, the uncoupling protein 1 (UCP1) increased in aBAT (axillary), cBAT (anterior cervical), iBAT (interscapular), nBAT (supraclavicular), and sBAT (suprascapular). The levels of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, were higher in cBAT and iBAT in the cold than in the warm group. The pAMPK/AMPK and pCREB/CREB were increased in cBAT and iBAT during cold acclimation, respectively. These data indicate that these different sites of BAT play the cold-induced thermogenic function for small mammals., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gut microbiota play a critical role in orchestrating metabolic homeostasis of the host. However, the crosstalk between host and microbial symbionts in small mammals are rarely illustrated. We used male Brandt's voles (Lasiopodomys brandtii) to test the hypothesis that gut microbiota and host neurotransmitters, such as norepinephrine (NE), interact to regulate energetics and thermogenesis during cold acclimation. We found that increases in food intake and thermogenesis were associated with increased monoamine neurotransmitters, ghrelin, short-chain fatty acids, and altered cecal microbiota during cold acclimation. Further, our pair-fed study showed that cold temperature can alter the cecal microbiota independently of overfeeding. Using cecal microbiota transplant along with β3-adrenoceptor antagonism and PKA inhibition, we confirmed that transplant of cold-acclimated microbiota increased thermogenesis through activation of cAMP-PKA-pCREB signaling. In addition, NE manipulation induced a long-term alteration in gut microbiota structure. These data demonstrate that gut microbiota-NE crosstalk via cAMP signaling regulates energetics and thermogenesis during cold acclimation in male Brandt's voles.

Ambient temperature is an important factor influencing many physiological processes, including antioxidant defense and immunity. In the present study, we tested the hypothesis that antioxidant defense and immunity are suppressed by high and low temperature treatment in Brandt's voles ( Lasiopodomys brandtii ). Thirty male voles were randomly assigned into different temperature groups (4, 23, and 32 °C, n =10 for each group), with the treatment course lasting for 27 d. Results showed that low temperature increased gross energy intake (GEI) and liver, heart, and kidney mass, but decreased body fat mass and dry carcass mass. With the decline in temperature, hydrogen peroxide (H 2 O 2 ) concentration, which is indicative of reactive oxygen species (ROS) levels, increased in the liver, decreased in the heart, and was unchanged in the kidney, testis, and small intestine. Lipid peroxidation indicated by malonaldehyde (MDA) content in the liver, heart, kidney, testis, and small intestine did not differ among groups, implying that high and low temperature did not cause oxidative damage. Similarly, superoxide dismutase (SOD) and catalase (CAT) activities and total antioxidant capacity (T-AOC) in the five tissues did not respond to low or high temperature, except for elevation of CAT activity in the testis upon cold exposure. Bacteria killing capacity, which is indicative of innate immunity, was nearly suppressed in the 4 °C group in contrast to the 23 °C group, whereas spleen mass and white blood cells were unaffected by temperature treatment. The levels of testosterone, but not corticosterone, were influenced by temperature treatment, though neither were correlated with innate immunity, H 2 O 2 and MDA levels, or SOD, CAT, and T-AOC activity in any detected tissues. Overall, these results showed that temperature had different influences on oxidative stress, antioxidant enzymes, and immunity, which depended on the tissues and parameters tested. Up-regulation or maintenance of antioxidant defense might be an important mechanism for voles to survive highly variable environmental temperatures.

Background: Huddling is highly evolved as a cooperative behavioral strategy for social mammals to maximize their fitness in harsh environments. Huddling behavior can change psychological and physiological responses. The coevolution of mammals with their microbial communities confers fitness benefits to both partners. The gut microbiome is a key regulator of host immune and metabolic functions. We hypothesized that huddling behavior altered energetics and thermoregulation by shaping caecal microbiota in small herbivores. Brandt's voles (Lasiopodomys brandtii) were maintained in a group (huddling) or as individuals (separated) and were exposed to warm (23 ± 1 °C) and cold (4 ± 1 °C) air temperatures (T a )., Results: Voles exposed to cold T a had higher energy intake, resting metabolic rate (RMR) and nonshivering thermogenesis (NST) than voles exposed to warm T a . Huddling voles had lower RMR and NST than separated voles in cold. In addition, huddling voles had a higher surface body temperature (T surface ), but lower core body temperature (T core ) than separated voles, suggesting a lower set-point of T core in huddling voles. Both cold and huddling induced a marked variation in caecal bacterial composition, which was associated with the lower T core . Huddling voles had a higher α and β-diversity, abundance of Lachnospiraceae and Veillonellaceae, but lower abundance of Cyanobacteria, Tenericutes, TM7, Comamonadaceae, and Sinobacteraceae than separated voles. Huddling or cold resulted in higher concentrations of short-chain fatty acids (SCFAs), particularly acetic acid and butyric acid when compared to their counterparts. Transplantation of caecal microbiota from cold-separated voles but not from cold-huddling voles induced significant increases in energy intake and RMR compared to that from warm-separated voles., Conclusions: These findings demonstrate that the remodeling of gut microbiota, which is associated with a reduction in host T core , mediates cold- and huddling-induced energy intake and thermoregulation and therefore orchestrates host metabolic and thermal homeostasis. It highlights the coevolutionary mechanism of host huddling and gut microbiota in thermoregulation and energy saving for winter survival in endotherms.

The maternal or paternal dietary composition can have important effects on various aspects of their offspring's physiology. Studies from animal models and humans showed that a maternal high-fiber diet protected offspring against fat accumulation. However, little is known about how a maternal low-fiber diet modifies the metabolism of offspring in herbivorous rodents. We hypothesized that a maternal low-fiber diet would confer long-lasting beneficial effects on offspring metabolic phenotypes in herbivorous Brandt's vole (Lasiopodomys brandtii). Female voles were fed either a control (12.4% fiber) or a low-fiber (3.5% fiber) diet throughout pregnancy and lactation, and all offspring were fed the control diet after weaning till 14 wk old. Offspring were sampled from each litter at 18 d and 14 wk of age. Another subset of adult offspring at 15 wk of age was fed a high-fat diet for 8 wk. We found that there was no difference in litter size, litter mass, or pup mass before weaning between the two maternal diet groups. Offspring from the maternal low-fiber diet increased energy intake, body mass, and lean mass; suppressed fat accumulation; and improved glucose tolerance compared with those from the control diet. Moreover, the maternal low-fiber diet alleviated high-fat diet-induced obesity in the adult offspring. Serum leptin concentration and uncoupling protein 1 content in brown adipose tissue of offspring were not affected by a maternal low-fiber diet. We demonstrate that herbivorous females fed a low-fiber diet during pregnancy and lactation may predispose their offspring to accelerated growth of lean tissue, which may increase the opportunity for survival and reproduction in offspring.

Brandt's voles have an annual cycle of body weight and adiposity. These changes can be induced in the laboratory by manipulation of photoperiod. In the present study, male captive-bred Brandt's voles aged 35 days were acclimated to a short day (SD) photoperiod (8L:16D) for 70 days. A subgroup of individuals (n=16) were implanted with transmitters to monitor physical activity and body temperature. They were then randomly allocated into long day (LD=16L:8D) (n=19, 8 with transmitters) and SD (n=18, 8 with transmitters) groups for an additional 70 days. We monitored aspects of energy balance, glucose and insulin tolerance (GTT and ITT), body composition and organ fat content after exposure to the different photoperiods. LD voles increased in weight for 35 days and then re-established stability at a higher level. At the end of the experiment LD-exposed voles had greater white adipose tissue mass than SD voles (P=0.003). During weight gain they did not differ in their food intake or digestive efficiency; however, daily energy expenditure was significantly reduced in the LD compared with SD animals (ANCOVA, P<0.05) and there was a trend to reduced resting metabolic rate RMR (P=0.075). Physical activity levels were unchanged. Despite different levels of fat storage, the GTT and ITT responses of SD and LD voles were not significantly different, and these traits were not correlated to body fatness. Hence, the photoperiod-induced obesity was independent on disruptions to glucose homeostasis, indicating a potential adaptive decoupling of these states in evolutionary time. Fat content in both the liver and muscle showed no significant difference between LD and SD animals. How voles overcome the common negative aspects of fat storage might make them a useful model for understanding the phenomenon of 'healthy obesity'., Competing Interests: The authors declare no competing or financial interests., (© 2016. Published by The Company of Biologists Ltd.)

Cold commonly affects growth and reproductive development in small mammals. Here, we test the hypothesis that low ambient temperature will affect growth and puberty onset, associated with altered hypothalamic Kiss-1 gene expression and serum leptin concentration in wild rodents. Male Brandt's voles (Lasiopodomys brandtii) were exposed to cold (4 ± 1 °C) and warm (23 ± 1 °C) conditions from the birth and sacrificed on different developmental stages (day 26, day 40, day 60, and day 90, respectively). Brandt's voles increased the thermogenic capacity of brown adipose tissue, mobilized body fat, decreased serum leptin levels, and delayed the reproductive development especially on day 40 in the cold condition. They increased food intake to compensate for the high energy demands in the cold. The hypothalamic Kiss-1 gene expression on day 26 was decreased, associated with lower wet testis mass and testis testosterone concentration on day 40, in the cold-exposed voles compared to that in the warm. Serum leptin was positively correlated with body fat, testis mass, and testosterone concentration. These data suggested that cold exposure inhibited hypothalamic Kiss-1 gene expression during the early stage of development, decreased serum leptin concentration, and delayed reproductive development in male Brandt's voles.

Maternal under- or over-nutrition not only alters neonatal body mass but also increases the risk of metabolic disorders in adulthood. Little is known about how maternal dietary protein affects offspring fitness in wild rodents. The present study was conducted to test the hypothesis that maternal dietary protein supplement has a long-term beneficial effect on offspring fitness in Brandt's vole (Lasiopodomys brandtii), a herbivorous rodent model. The vole dams were fed either a control (18% protein) or high-protein (36% protein) diet throughout pregnancy and lactation. After weaning, all offspring received a control diet till 14 weeks old. Energetic parameters, serum leptin concentration and glucose tolerance were measured. The adult offspring were fed high-fat diet for 8 weeks, and body weight and food intake were measured. No difference was observed in litter size, litter mass or pup mass before weaning. Maternal protein supplement increased body mass and the mass of reproductive organ but decreased digestibility and fat deposition and alleviated HFD-induced obesity especially in the males. Glucose tolerance was elevated in the offspring from maternal protein supplement, especially in the females. The accelerated growth may be associated with high serum leptin concentration at weaning, a state of leptin resistance, and the low digestibility may predispose obesity resistance especially in male offspring from maternal high-protein diet. These data demonstrate that maternal protein supplement confers the long-term sex-specific beneficial consequences of accelerated growth and improved obesity resistance and glucose tolerance of their offspring., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Small mammals inhabiting temperate and arctic regions exhibit annual adaptive adjustments in physiology, anatomy, and behavior. No data on the physiology of Maximowicz's voles (Microtus maximowiczii) are available at present. Here we examined the seasonal changes in body mass, food intake, thermogenic capacity, serum leptin and thyroid hormone levels in wild-captured individuals from Inner Mongolian grassland, China. We further examined the effects of photoperiod on these parameters. Energy intake, resting metabolic rate, nonshivering thermogenesis (NST), and serum tri-iodothyronine (T3) levels increased while serum leptin and body mass decreased in the cold seasons. Serum T3 levels were positively correlated with NST and uncoupling protein 1 (UCP1) contents in brown adipose tissue, and leptin levels were negatively correlated with energy intake and resting metabolic rate. Furthermore, laboratory data showed these changes could be induced by short photoperiod alone. Taken together, our results indicate that Maximowicz's voles can increase thermogenic capacity and energy intake to cope with cold stress. Serum leptin seems to be involved in the regulation of energy intake and changes in T3 level may be important for the variations in NST and/or UCP1. Short photoperiod can serve as a seasonal cue for the winter acclimatization of energy balance in free-living Maximowicz's voles.

Life history theory assumes there are trade-offs between competing functions such as reproduction and immunity. Although well studied in birds, studies of the trade-offs between reproduction and immunity in small mammals are scarce. Here we examined whether reduced immunity is a consequence of reproductive effort in lactating Brandt's voles (Lasiopodomys brandtii). Specifically, we tested the effects of lactation on immune function (Experiment I). The results showed that food intake and resting metabolic rate (RMR) were higher in lactating voles (6≤ litter size ≤8) than that in non-reproductive voles. Contrary to our expectation, lactating voles also had higher levels of serum total Immunoglobulin G (IgG) and anti-keyhole limpet hemocyanin (KLH) IgG and no change in phytohemagglutinin (PHA) response and anti-KLH Immunoglobulin M (IgM) compared with non-reproductive voles, suggesting improved rather than reduced immune function. To further test the effect of differences in reproductive investment on immunity, we compared the responses between natural large (n≥8) and small litter size (n≤6) (Experiment II) and manipulated large (11-13) and small litter size (2-3) (Experiment III). During peak lactation, acquired immunity (PHA response, anti-KLH IgG and anti-KLH IgM) was not significantly different between voles raising large or small litters in both experiments, despite the measured difference in reproductive investment (greater litter size, litter mass, RMR and food intake in the voles raising larger litters). Total IgG was higher in voles with natural large litter size than those with natural small litter size, but decreased in the enlarged litter size group compared with control and reduced group. Our results showed that immune function is not suppressed to compensate the high energy demands during lactation in Brandt's voles and contrasting the situation in birds, is unlikely to be an important aspect mediating the trade-off between reproduction and survival.

Maternal serum leptin concentrations have been suggested as a key factor in programming growth patterns and protecting against adult metabolic disease in human offspring. However, the role of maternal leptin in the development of wild rodent offspring is not clear. We tested the hypothesis that maternal hyperleptinemia in lactating Brandt's voles (Lasiopodomys brandtii) can protect their offspring from the risks of high-fat-diet-induced-obesity and insulin resistance. Lactating voles were supplemented with murine leptin (0.64 μg g(-1 ) day(-1)) or phosphate-buffered saline (control) on days 10-17 of lactation (peak lactation). At 12 weeks of age, the female and male offspring of the two maternal groups were randomly assigned to two groups each and fed either a high-fat diet (41% of gross energy as fat) or a control diet (14% of gross energy as fat) until the age of 23 weeks. Body mass, food intake, glucose tolerance and resting metabolic rate were determined in the four offspring groups. After animals were sacrificed, organ masses and adipose tissue distribution, and serum leptin and insulin concentrations were measured. Offspring of leptin-treated mothers showed no significant differences in body mass, energy intake or energy expenditure, body composition, glucose tolerance or serum leptin and insulin concentrations from offspring of control mothers. The high-fat diet induced increases in body mass (by 23% in female and 17% in male offspring) and reduced glucose tolerance in both female and male offspring, indicative of the emergence of insulin resistance, even though digestible energy intake of the male offspring decreased on the high-fat diet. These results indicate that maternal hyperleptinemia during peak lactation in Brandt's voles did not protect against diet-induced obesity or glucose intolerance in their offspring.

Background: Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10-12) and small (3-4) litter sizes, of Brandt's voles (Lasiopodomys brandtii), a rodent species from Inner Mongolia grassland in China., Methodology/principal Findings: Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb) mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3) mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP) mRNA increased in the offspring from small litters., Conclusions/significance: These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

Basal metabolic rate (BMR) has been shown to be a highly flexible phenotypic trait both between and within species, but the physiological, biochemical and molecular mechanisms are still unclear. Brandt's voles (Lasiopodomys brandtii) and Mongolian gerbils (Meriones unguiculatus) are two sympatric rodent species in Inner Mongolian grasslands of China. It has been shown that Brandt's voles have higher metabolic rate than Mongolian gerbils. In this study, we elucidated the inter-specific variation in BMR integratively from the molecular levels to whole organism. Our results showed that differences in organ mass were not good predictors for the observed variations in BMR, while variations in the activity of thyroid hormones and the metabolic biochemical markers of tissues, such as mitochondria density, cytochrome c oxidase activity and state 4 respiration, were strongly correlated with variations in BMR, and there was also a positive relationship between residuals of T(3)/T(4) and state 4 respiration, suggesting that thyroid hormones play an important role in the determination of BMR variations., (Copyright 2010 Elsevier Inc. All rights reserved.)

To test the hypothesis that mammals that show decrease in body mass under short-day condition should be resistant to high-fat induced obesity, we traced the changes of energy balance in a wild rodent, Brandt's voles (Lasiopodomys brandtii), which were acclimated to either long day (16L: 8D, LD) or short day (8L: 16D, SD) and fed either low-fat diet (LFD) or high-fat diet (HFD) in each photoperiodic manipulation. We found that Brandt's vole was not resistant to high-fat diet-induced obesity and SD, not HFD, induced the elevation in basal metabolic rate, the maximal rate of oxygen consumption after norepinephrine injection, and uncoupling protein 1 content in brown adipose tissue. HFD caused the increase in apparent digestibility and body fat mass, and the decrease in energy intake in both LD and SD voles. The enhancement of energy absorption associated with small intestine tissue recruitment can compensate the lower energy intake, which may contribute to the high-fat diet-induced body fat deposition. Thus, a decrease in body-weight gain but has no resistance to high-fat induced obesity implies an evolutionary and adaptive mechanism which is a benefit for their winter survival.

Brandt's voles Lasiopodomys brandtii exhibit large increases in nonshivering thermogenesis to cope with chronic cold exposure, resulting in compensatory hyperphagia and fat mobilization. These physiological events are accompanied by a remarkable reduction in serum leptin levels. However, the role of hypoleptinemia in cold adaptation in this species is still unknown. In the present study, we tested the hypothesis that hypoleptinemia contributes to increases in food intake and brown adipose tissue (BAT) thermogenesis by modifying hypothalamic neuropeptides in cold-exposed Brandt's voles. Adult male voles were transferred to 5 degrees C for 28 days. Accompanied by a decrease in serum leptin levels, hypothalamic agouti-related protein (AgRP) mRNA levels were significantly increased, but there were no changes in the long form of leptin receptor (Ob-Rb), suppressor of cytokine signaling 3 (SOCS3), neuropeptide Y (NPY) mRNA, proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated peptide (CART) mRNA levels in the hypothalamus. When cold-exposed voles were returned to warm (23 degrees C) for 28 days, body mass, food intake, serum leptin, and AgRP mRNA were restored to control levels. Leptin administration in cold-exposed voles decreased food intake as well as hypothalamic AgRP mRNA levels. There were no significant effects of leptin administration on hypothalamic Ob-Rb, SOCS3, NPY, POMC, CART mRNA, and uncoupling protein 1 levels under cold conditions. These results suggest that hypoleptinemia partially contributes to cold-induced hyperphagia, which might involve the elevation of hypothalamic AgRP gene expression.

The maximum rate of sustained energy intake (SusEI) may limit reproductive effort, thermoregulatory capability and other aspects of an animal's energy expenditure. Consequently, factors that limit SusEI are of interest. The ;heat dissipation limitation hypothesis' suggests that maximum SusEI during lactation is limited by the capacity to dissipate body heat generated as a by-product of processing food and producing milk. In the present study, we tested the heat dissipation limitation hypothesis in lactating Brandt's voles (Lasiopodomys brandtii). Female voles were mated and pregnant at 21(+/-1) degrees C. A random sample of animals was transferred into a hot room 30(+/-1) degrees C on the day of parturition. The energy intake of lactating voles at 30 degrees C was always lower than that at 21 degrees C. At peak lactation food intake was 3.3 g day(-1) lower at 30 degrees C than at 21 degrees C. There was no significant difference in digestibility. With similar mean litter sizes (7.26+/-0.46 pups at 21 degrees C and 7.78+/-0.39 pups at 30 degrees C at the beginning of parturition, 6.83+/-0.51 pups at 21 degrees C and 7.73+/-0.50 pups at 30 degrees C at weaning), the milk energy output of mothers, evaluated from the difference between metabolizable energy intake and daily energy expenditure measured by doubly labelled water, at 30 degrees C was 23.3 kJ day(-1) lower than that at 21 degrees C on days 14-16 of lactation. As for reproductive performance, there was a difference in the response to the higher temperature between mothers raising large and those raising small litters. For small litters (<7) there was no significant change in litter mass, but for large litters (

In order to evaluate the potential costs of humoral immune response, which is important for survival in small wild mammals, we studied the physiological function of adult male Brandt's voles (Lasiopodomys brandtii) challenged with human immunoglobulin G (IgG). Compared with controls, the immunochallenged voles showed significantly higher antibody levels 15 days after injection. Serum testosterone levels, and mass of testes and epididymides were lower in immunochallenged voles than in control animals. Body mass remained stable during the course of the experiment. Total and digestible energy intake showed a transient decrease following IgG injection, while resting metabolic rate (RMR) increased. Taken together, these data suggest a shift in metabolic priorities in response to immune challenge. Our results provide evidence that mounting a humoral immune response to an immunological challenge may have fitness costs in male Brandt's voles.

In most mammals, maternal body mass and fat mass increase during pregnancy due to hyperphagia. These physiological changes provide the fetus with energy and nutrients and prepare the mother for the high energetic demands of lactation. In the present study, metabolic changes in response to cold and pregnancy were examined in female Brandt's voles (Lasiopodomys brandtii). At 23+/-1 degrees C, the voles increased body mass and deposited body fat during pregnancy. However, at 5+/-1 degrees C pregnant voles did not deposit body fat even though energy intake increased above the level in the warm. Serum leptin concentration increased during pregnancy and was not influenced by cold exposure. Thermogenic capacity, as indicated by uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT), increased in cold-exposed pregnant voles. The number and mass of fetuses were not affected by cold exposure. Our data may indicate the importance of an increased serum leptin concentration for a successful outcome of the pregnancy and also the independence of leptin secretion from body fat in pregnant voles. It also implies the need to develop central leptin resistance with respect to control of energy balance for pregnant voles.

Reproduction, especially lactation, is associated with major metabolic adaptive changes. In this study, we investigated the metabolic changes and the roles of leptin during different periods of reproduction in primiparous Brandt's voles (Lasiopodomys brandtii). Energy intake, thermogenic capacity and serum leptin levels were examined in non-reproductive, mid pregnant, late pregnant, early lactating and peak lactating voles. Voles increased body mass by nearly 70% during late pregnancy compared to the non-breeding controls. The increase in body mass was mainly due to the increase in body fat mass which increased by 56%, and the growth of the reproductive tissues and digestive organs. Lactating voles decreased body fat by nearly 27% at peak lactation compared to the controls, and 53% compared to late pregnant voles. At the same time they increased food intake significantly. Uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT) decreased significantly at peak lactation. Serum leptin increased significantly in the mid pregnancy, at a time when there was no increase in body fat, and remained at this high level in late pregnancy. Leptin levels decreased after parturition and reached a nadir at peak lactation. Serum leptin was negatively correlated with energy intake during lactation, but not during pregnancy. These data suggest that Brandt's voles adjust energy intake, thermogenic capacity and body reserves to match the high energy demands for reproduction. Hyperleptinemia, without decreased energy intake suggests a state of leptin resistance during pregnancy, and hypoleptinemia during lactation might act as a signal to stimulate energy intake.

Leptin acts within the hypothalamus to diminish food intake. In Brandt's voles (Lasiopodomys brandtii), both circulating leptin levels and food intake are elevated during pregnancy, suggesting an ineffectiveness of leptin to reduce food intake. Diminished hypothalamic leptin receptors and impaired leptin signal transduction are characteristic of central leptin resistance. The present study aimed to determine whether these characteristic modulations of leptin sensitivity occurred in pregnant Brandt's voles. The mRNA expression of the long form of the leptin receptor (Ob-Rb), suppressor-of-cytokine-signalling 3 (SOCS3), neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus were examined on dioestrous, day 5, day 10 and day 18 of pregnancy. Compared to controls, there was no significant change in hypothalamic Ob-Rb mRNA during the pregnancy. SOCS3 mRNA was increased significantly by 68% on day 10% and 93% on day 18 of pregnancy compared to controls. Despite elevated leptin levels, POMC mRNA was decreased significantly by 60% on day 18 of pregnancy, whereas no differences were found in the mRNA expression of NPY, AgRP and CART in pregnant voles compared to controls. The elevation of SOCS3 mRNA together with disrupted leptin regulation of neuropeptides in the hypothalamus suggests that leptin resistance may develop in pregnant Brandt's voles.

Many small mammals respond to seasonal changes in photoperiod via alterations in morphology, physiology and behaviour. In the present study, we tested the hypothesis that the preweaning (from embryo to weaning) photoperiod experience can affect subsequent development in terms of body mass and thermogenesis. Brandt's voles (Lasiopodomys brandtii) were gestated and reared to weaning under either a short (SD, 8 h:16 h L:D) or a long photoperiod (LD, 16 h:8 h L:D) at a constant ambient temperature (23 degrees C). At weaning, male juveniles were either maintained in their initial photoperiod or transferred to the alternative photoperiod for 8 weeks. Postweaning SD voles had a lower body mass but higher thermogenic capacity compared with LD voles. At the same time, preweaning photoperiod conditions had long-lasting effects on thermogenic capacity later in life. Serum leptin concentration was positively correlated with body mass and body fat mass, whereas it was negatively correlated with energy intake and uncoupling protein 1 content in brown adipose tissue. Our results suggest that postweaning development in terms of body mass and thermogenesis is predominantly influenced by the postweaning photoperiod, while the preweaning photoperiod experience could chronically modify thermogenesis but not body mass. Furthermore, serum leptin, acting as a potential adipostatic signal, may be involved in the regulation of both energy intake and energy expenditure.

Food quality and availability play an important role in an animal's life history. The aim of this study was to examine the effect of diet quality [high-fiber diet (HF) or low-fiber diet (LF)] on energy budgets and thermogenesis in Brandt's voles (Lasiopodomys (Microtus) brandtii). Dry matter intake and gross energy intake increased and digestibility decreased in HF voles compared with LF voles, while the digestible energy intake was similar for both HF and LF voles. Nonshivering thermogenesis (NST) decreased in HF voles, while LF voles kept stable; no significant differences were detected in basal metabolic rate (BMR), BAT uncoupling protein 1 (UCP1) content and the levels of serum thyroid hormones (T3 and T4) between HF and LF voles. Although there were no differences in body fat content and serum leptin concentrations between HF and LF voles, serum leptin concentrations in HF voles were reduced to nearly half as those seen in LF voles after 4-weeks acclimation. These results support the hypothesis that Brandt's voles can compensate the poor quality diet physiologically by the means of increasing food intake and decreasing thermogenesis.

Environmental factors play an important role in the seasonal adaptation of body mass and thermogenesis in wild small mammals. In this study, we performed a factorial experiment (temperature x photoperiod) in which Brandt's voles and Mongolian gerbils were acclimated to different photoperiods (long photoperiod, 16L : 8D; short photoperiod, 8L : 16D) and temperatures (warm, 23 degrees C; cold, 5 degrees C) to test the hypothesis that photoperiod, temperature, or both together can trigger seasonal changes in serum leptin level, body mass, thermogenesis, and energy intake. Our data demonstrate that Brandt's voles showed a remarkable decrease in body mass in both the cold and a short photoperiod. However, no significant changes in body mass were found for gerbils exposed to similar conditions. The short photoperiod induced a decrease in serum leptin levels for both voles and gerbils that might contribute to an increase in energy intake. Furthermore, the short photoperiod induced an increase of uncoupling protein 1 (UCP1) content for both voles and gerbils, and cold can further enhance the increase in voles. No interactions between photoperiod and temperature were detected for the two species. Brandt's voles can decrease their body mass through changes in energy intake and expenditure, while Mongolian gerbils can keep body mass relatively stable by balancing energy metabolism under winterlike conditions. Leptin was potentially involved in the regulation of body mass and thermogenic capacity for the two species.

Ingestion of soft faeces derived from caecal contents, caecotrophy, in herbivorous small mammals is considered an adaptation to the metabolic disadvantage of small body size, especially when feeding on diets of low quality. We investigated daily activity patterns in captive Brandt's voles (Lasiopodomys brandtii), including feeding, locomotion, caecotrophy, and defaecation, by continuous 24 h visual observation; and estimated the contribution of soft faeces ingestion (caecotrophy) to intake of protein and energy. Brandt's voles ingested 68.8 +/- 7.4 fecal pellets per day, averaging 17 +/- 2% of total faeces produced. The amount of faeces ingested did not differ between female and male voles or between night and day time. All animals showed average 3 h ultradian cycles in behaviour during the course of the day and night. The contributions of caecotrophy to the dietary intake of crude protein and metabolizable energy were estimated respectively as 9 and 8% on a high-protein, easily digested commercial rabbit pellet diet. However, the importance of caecotrophy to the field voles is likely to be higher on a natural diet of lower nutrient density. The rhythm of caecotrophy in voles depended mainly on the rhythm of the colonic separation mechanism in the proximal colon and passage in the distal colon, and may be regulated by feeding and other activity rhythms. Ultradian rhythms in caecotrophy helped to minimise potential conflicts in utilizing the gut, especially in balancing the caecal fermentation and salvaging nutrients contained in caecal bacteria.

Social status can influence an animal's immune and reproductive functions, eventually leading to alterations in immunocompetence and reproductive success. Here, we report that rank assessed in a food competition test, considered as an index of social status, has significant influences on humoral immune functions in male Brandt's voles (Lasiopodomys brandtii) living in a group. Our data reveal a negative correlation of the spleen mass and serum antibody levels with social status, as well as a positive correlation of serum cortisol levels with social status. Males winning in food competition had a smaller spleen, a lower level of serum antibodies, and a higher level of serum cortisol than did their conspecific counterparts. These data indicate interactions between social status and humoral immune functions and might illustrate a trade-off between infection risks and reproductive success in male Brandt's voles.

Lactation is the most energetically expensive period for mammals and is associated with increased metabolism and energy intake, but decreased thermogenic capacity. It is well known that small mammals increase both food intake and thermogenesis in the cold. The present study aimed to examine whether Brandt's voles Lasiopodomys brandtii could adjust energy intake and thermogenesis to accommodate simultaneous lactation and cold exposure. The voles were placed into two temperature treatments: warm (23+/-1 degrees C) and cold (5+/-1 degrees C). Animals at each temperature treatment were further divided into two groups: non-reproductive (NR) and lactating females. We found that lactating voles at peak lactation in the cold enhanced food intake by 2.6 g day(-1) compared with those in the warm, and increased uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT), to the same level as the cold-exposed NR females. Serum leptin levels decreased significantly during lactation and were positively correlated with body mass and fat mass. After correcting for the effects of body mass, residual serum leptin was negatively correlated with residual gross energy intake and residual RMR. In addition, residual serum leptin levels were positively correlated with UCP1 contents in the warm, but not in the cold. Together, these data suggest that lactating voles can increase thermogenic capacity and energy intake to meet the high energetic costs of simultaneous lactation and cold exposure. Further, serum leptin appears to be involved in the energy intake regulation and thermoregulation, but the thermoregulation in the cold may be mainly mediated by other factors.

This study examined the effects of photoperiod (long day [16 Light:8 Dark] and short day [8 Light:16 Dark]), temperature (cold [5 degrees C] and warm [23 degrees C]), and diet quality (high-fiber diet [36% neutral-detergent fiber (NDF)] and low-fiber diet [23% NDF]) on basal metabolic rate (BMR), digestible energy intake, and organ size in the Brandt's vole (Lasiopodomys brandtii). Cold increased BMR and showed a significant interaction with diet quality. Cold and short photoperiod increased intake of food and digestible energy. The high-fiber diet increased food intake, but decreased digestibility, and had no effects on digestible energy intake. Voles housed in the cold had heavier liver, kidneys and gastrointestinal segments but a lighter carcass. Segments of the gastrointestinal tract tended to be heavier when voles were fed the high-fiber diet. Voles housed in short photoperiod had lighter heart and kidneys but heavier gut segments. With the effects of body mass on BMR and organs was removed, BMR was significantly related to the dry mass of heart, liver, kidneys and cecum. Digestible energy intake was significantly related to the dry mass of kidneys and stomach. These significant relationships were also detected after removing the effects of body mass, temperature, photoperiod and diet quality. There was also a significant correlation between BMR and digestible energy intake. Our results suggest that variations in BMR reflected the evolution of metabolic machinery that induces higher energy intakes. The data also support the assimilation capacity model of endothermy.

The present study was designed to examine whether photoperiod alone was effective to induce seasonal regulations in physiology in root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau noted for its extreme cold environment. Root voles were randomly assigned into either long photoperiod (LD; 16L:8D) or short photoperiod (SD; 8L:16D) for 4 weeks at constant temperature (20 degrees C). At the end of acclimation, SD voles showed lower body mass and body fat coupled with higher energy intake than LD voles. SD greatly enhanced thermogenic capacities in root voles, as indicated by elevated basal metabolic rate (BMR), nonshivering thermogenesis (NST), mitochondrial protein content and uncoupling protein-1 (UCP1) content in brown adipose tissue (BAT). Although no variations in serum leptin levels were found between SD and LD voles, serum leptin levels were positively correlated with body mass and body fat mass, and negatively correlated with energy intake and UCP1 content in BAT, respectively. To summarize, SD alone is effective in inducing higher thermogenic capacities and energy intake coupled with lower body mass and body fat mass in root voles. Leptin is potentially involved in the photoperiod induced body mass regulation and thermogenesis in root voles.

Survival of small mammals in winter requires proper adjustments in physiology, behavior and morphology. The present study was designed to examine the changes in serum leptin concentration and the molecular basis of thermogenesis in seasonally acclimatized root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau. In January root voles had lower body mass and body fat mass coupled with higher nonshivering thermogenesis (NST) capacity. Consistently, cytochrome c oxidase activity and mitochondrial uncoupling protein-1 (UCP1) protein contents in brown adipose tissues were higher in January as compared to that in July. Circulating level of serum leptin was significantly lower in winter and higher in July. Correlation analysis showed that serum leptin levels were positively related with body mass and body fat mass while negatively correlated with UCP1 protein contents. Together, these data provided further evidence for our previous findings that root voles from the Qinghai-Tibetan plateau mainly depend on higher NST coupled with lower body mass to enhance winter survival. Further, fat deposition was significantly mobilized in cold winter and leptin was potentially involved in the regulation of body mass and thermogenesis in root voles. Serum leptin might act as a starvation signal in winter and satiety signal in summer.

Environmental cues play important roles in the regulation of an animal's physiology and behavior. The purpose of the present study was to test the hypothesis that ambient temperature was a cue to induce adjustments in body mass, energy intake and thermogenic capacity, associated with changes in serum leptin levels in Brandt's voles (Lasiopodomys brandtii). We found that Brandt's voles increased resting metabolic rate (RMR) and energy intake and kept body mass stable when exposed to the cold while showed a significant increase in body mass after rewarming. The increase in body mass after rewarming was associated with the higher energy intake compared with control. Uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT) increased in the cold and reversed after rewarming. Serum leptin levels decreased in the cold while increased after rewarming, associated with the opposite changes in energy intake. Further, serum leptin levels were positively correlated with body mass and body fat mass. Together, these data supported our hypothesis that ambient temperature was a cue to induce changes in body mass and metabolism. Serum leptin, as a starvation signal in the cold and satiety signal in rewarming, was involved in the processes of thermogenesis and body mass regulation in Brandt's voles.

Photoperiod cues play important roles in the regulation of seasonal variations in body mass (BM) and energy balance for many small mammals. The present study was designed to examine the effects of photoperiod acclimation on BM, energy intake, and serum leptin levels in Brandt's voles (Microtus (Lasiopodomys) brandtii). After 4 weeks of acclimation to either long (LD; light:dark, 16:8) or short (SD; 8:16) photoperiod, SD voles had lower BM, body fat mass, and dry mass of liver and kidneys, but higher digestible energy intake in comparison to LD voles. SD voles also showed a lower level of serum leptin than did LD voles. Furthermore, the level of serum leptin was correlated positively with body fat mass and negatively with gross energy intake. Together, these data suggest that Brandt's voles employ a strategy of minimizing body growth, increasing energy intake, and mobilizing fat deposition in response to cues associated with short photoperiod. Furthermore, leptin seems to be involved in the regulation of BM and energy balance mediated by photoperiod.

Seasonal changes in an animal's morphology, physiology, and behavior are considered to be an adaptive strategy for survival and reproductive success. In the present study, we examined body weight and several behavioral, physiological, hormonal, and biochemical markers in seasonally acclimatized Brandt's voles (Microtus brandti) to test our hypothesis that Brandt's voles can decrease energy intake associated with decrease in body weight, body fat content, serum leptin level, and increasing thermogenesis in winter conditions. We found that the body weight of Brandt's voles was lowest in winter (December to February) and highest in spring and early summer (May to June). This seasonal variation in body weight was associated with changes in other markers examined. For example, the winter decrease in body weight was accompanied by increased energy intake and enhanced nonshivering thermogenesis (NST) as well as by decreased body fat mass and reduced levels of circulating leptin. Further, circulating levels of leptin were positively correlated with body weight and body fat mass, and negatively correlated with energy intake and uncoupling protein 1 contents. Together, these data do not support our hypothesis and suggest that leptin may be involved in this process and serve as a starvation signal in Brandt's voles.

Digestive performance, gut morphology and rate of digesta passage were measured in Brandt's voles (Microtus brandti) offered pelleted diets of low (25% neutral-detergent fibre) and high (38%) fibre content. Digestion coefficients of dry matter, crude fat, crude protein, energy and fibre were all significantly lower on the higher fibre diet. Although not significantly higher, dry matter intakes were more than maintained when extra cellulose was included in the diet, so that intakes of digestible energy were only 22% lower on the higher fibre diet. Total length and total gut tissue weight increased significantly, and the length and tissue weight of the caecum, proximal colon, and distal colon were significantly greater on the higher fibre diet as well. Total tract mean retention time (MRT) of a solute marker (Co-EDTA) was significantly greater than that of a particle marker (Cr-cell walls) on the lower fibre diet, and in the same direction on the higher fibre diet. The ratio of solute to particle MRTs (the solute/particle differential retention ratio) was 1.45 on the lower fibre diet and 1.19 on the higher fibre diet. There were no significant differences in marker MRTs between diets. Examination of marker concentrations in the stomach, small intestine, caecum and colon of voles killed at 0.5-h intervals after a pulse dose of Co-EDTA indicated that the marker was recycled to the stomach by coprophagy. Thus, as in other microtine rodents, an increase in gut capacity, selective digesta retention and recycling of digesta via coprophagy enables Brandt's voles to utilise diets of higher fibre content than may be expected for such a small (45 g) mammalian herbivore.