Reduction In Metabolic Rate Research Articles

Climatic cues and glucocorticoids in a free-ranging riparian population of red deer (Cervus elaphus)

We measured faecal cortisol metabolites of a free-ranging riparian population of red deer to investigate potential effects of season, ambient temperature, precipitations and water level on the annual secretion pattern. Individuals may cope with environmental challenges through the secretion of stress hormones (glucocorticoids) which allows the integration of environmental change and life history traits by means of an adaptive feedback mechanism. Adaptations regard cyclic day-to-day activities, short-term environmental stressors or long-term ecological pressures. We detected a clear seasonal pattern of glucocorticoid metabolites secretion, with higher levels in winter and lower levels in summer. The model relating glucocorticoids secretion to minimum ambient temperature was the best fit to our dataset, although the observed pattern might as well be due to declining nutritional intake and reduction of metabolic rate in the cold season. We observed an improvement of the fit when stochastic events (flash flood) were included in the model, and discussed their role as potential contingent environmental stressors.

Long-term caloric restriction reduces metabolic rate and heart rate under cool and thermoneutral conditions in FBNF1 rats

The long-term metabolic and cardiovascular responses to caloric restriction (CR) are poorly understood. We examined the responses to one year of CR in FBNF1 rats housed in cool (COOL; Ta=15°C) or thermoneutral (TMN; Ta=30°C) conditions. Rats were acclimated to COOL or TMN for 2 months, instrumented for cardiovascular telemetry and studied in calorimeters. Baseline caloric intake, oxygen consumption (VO2), mean arterial blood pressure (MAP), and heart rate (HR) were determined prior to assignment to ad lib (AL) or CR groups (30–40% CR) within each Ta (n=8). Groups of rats were studied after 10 weeks CR, one year CR, and after 4 days of re-feeding. Both 10 weeks and one year of CR reduced HR and VO2 irrespective of Ta. Evaluation of the relationship between metabolic organ mass (liver, heart, brain, and kidney mass) and energy expenditure revealed a clear shift induced by CR to reduce expenditure per unit metabolic mass in both COOL and TMN groups. Re-feeding resulted in prompt elevations of HR and VO2 to levels observed in control rats. These findings are consistent with the hypothesis that long term CR produces sustained reductions in metabolic rate and heart rate in rats.

Microcystin-LR: How it affects the cardio-respiratory responses to hypoxia in Nile tilapia, Oreochromis niloticus

The effects of microcystin on the cardio-respiratory function of Nile tilapia were analyzed 48h after intraperitoneal injection of microcystin-LR (MC-LR – 100μgkg−1body weight). Exposure to MC-LR induced significant reduction in metabolic rate (V˙O2) and increase in the critical O2 tension (PCO2) in relation to the control group. Gill ventilation (V˙G) and ventilatory tidal volume (VT) were considerably lower in fish exposed to MC-LR, probably due to an alteration in the homeostatic mechanisms, impairing the regular respiratory response of this species to environmental hypoxia. The ability to maintain the O2 extraction from the ventilatory current (EO2) during severe hypoxia was also significantly reduced in fish exposed to MC-LR exposure. Control fish displayed the characteristic reflex bradycardia in response to hypoxia. However, when compared to the control group, fish exposed to MC-LR presented significantly lower heart rate (fH) in normoxia and in all experimental hypoxic levels, probably due to a direct effect of this toxin on the cardiac tissue.

Vascular and Metabolic Response to Bevacizumab-Containing Regimens in Two Patients With Colorectal Liver Metastases Measured by Dynamic Contrast-Enhanced MRI and Dynamic 18F-FDG-PET

Early monitoring of response to treatment is one of the cornerstones of personalized treatment. As new and often expensive targeted therapies, which are tumoristatic rather than tumoricidal, become available, new demands are posed on response assessment. Bevacizumab, an antiangiogenic agent causing normalization of the tumor microvasculature, potentiates the effect of cytotoxic agents on colorectal liver metastases. It is known that assessment of glucose metabolism by (dynamic) positron emission tomography using [(18)F]-2-fluoro-2-deoxy-D-glucose ((18)F-FDG PET) can be used as an early surrogate endpoint to determine treatment efficacy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to quantify functional tumor vasculature (permeability, vascular surface area). Here, we describe the response of colorectal liver metastases to cytotoxic regimens including bevacizumab using both (18)F-FDG PET and DCE-MRI in 2 cases. In both cases, a large reduction in glucose metabolic rate and functional tumor vasculature are observed after 3 treatment cycles.

Thermoregulation of tree-dwelling temperate bats — a behavioural adaptation to force live history strategy

Metabolic rate and body temperature (Tb) reduction during torpor can provide significant energy savings for bats during inclement weather and food scarcity. However, torpor use may slow down biochemical processes including fetal and juvenile development and sperm production. Sex-differences in the timing of reproductive activity of bats in the temperate climate zone should result in differences of the thermoregulation behaviour by males and females during summer. To test this hypothesis, we studied thermoregulation of free-ranging, tree-dwelling gleaning bats (Myotis bechsteinii) and trawling bats (M. daubentonii) during different reproductive periods. Gleaners and trawlers are able to forage on prey which is sitting on vegetation and the ground (gleaning) or which is slowly moving over water bodies (trawling). This prey is characterized by lower ambient temperature (Ta) dependent abundance than flying prey. We used temperature-sensitive radio transmitters to measure skin temperature (Tsk). Temperature telemetry over 144 census days revealed a significant effect of reproductive period and sex on Tsk. Pre-spermatogenic males exhibited a significantly greater Tsk reduction than females in early pregnancy. Males at the beginning of sperm production and in main spermatogenesis exhibited much more frequent and deeper temperature reductions than females in late pregnancy and in lactation. Lactating females maintained the highest Tsk of all bats. Post-lactating females reduced Tsk to the same extent or even more than males in advanced spermatogenesis.Our findings indicate that the thermoregulation of gleaning and trawling temperate bats is likely to be much less influenced by environmental conditions than that of aerial hawking bat species. We suggest that both sexes of Bechstein's bats and Daubenton's bats primarily adapt their thermoregulation in response to current reproductive activity.

Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to Obesity

Free fatty acids (FFAs) suppress appetite when injected into the hypothalamus. To examine whether lipoprotein lipase (LPL), a serine hydrolase that releases FFAs from circulating triglyceride (TG)-rich lipoproteins, might contribute to FFA-mediated signaling in the brain, we created neuron-specific LPL-deficient mice. Homozygous mutant (NEXLPL-/-) mice were hyperphagic and became obese by 16weeks of age. These traits were accompanied by elevations in the hypothalamic orexigenic neuropeptides, AgRP and NPY, and were followed by reductions in metabolic rate. The uptake of TG-rich lipoprotein fatty acids was reduced in the hypothalamus of 3-month-old NEXLPL-/- mice. Moreover, deficiencies in essential fatty acids in the hypothalamus were evident by 3months, with major deficiencies of long-chain n-3 fatty acids by 12months. These results indicate that TG-rich lipoproteins are sensed in the brain by an LPL-dependent mechanism and provide lipid signals for the central regulation of body weight and energy balance.

Influence of dietary state and insulin on myocardial, skeletal muscle and brain [18F]-fluorodeoxyglucose kinetics in mice

BackgroundWe evaluated the effect of insulin stimulation and dietary changes on myocardial, skeletal muscle and brain [18F]-fluorodeoxyglucose (FDG) kinetics and uptake in vivo in intact mice.MethodsMice were anesthetized with isoflurane and imaged under different conditions: non-fasted (n = 7; "controls"), non-fasted with insulin (2 IU/kg body weight) injected subcutaneously immediately prior to FDG (n = 6), fasted (n = 5), and fasted with insulin injection (n = 5). A 60-min small-animal PET with serial blood sampling and kinetic modeling was performed.ResultsWe found comparable FDG standardized uptake values (SUVs) in myocardium in the non-fasted controls and non-fasted-insulin injected group (SUV 45-60 min, 9.58 ± 1.62 vs. 9.98 ± 2.44; p = 0.74), a lower myocardial SUV was noted in the fasted group (3.48 ± 1.73; p < 0.001). In contrast, the FDG uptake rate constant (Ki) for myocardium increased significantly by 47% in non-fasted mice by insulin (13.4 ± 3.9 ml/min/100 g vs. 19.8 ± 3.3 ml/min/100 g; p = 0.030); in fasted mice, a lower myocardial Ki as compared to controls was observed (3.3 ± 1.9 ml/min/100 g; p < 0.001). Skeletal muscle SUVs and Ki values were increased by insulin independent of dietary state, whereas in the brain, those parameters were not influenced by fasting or administration of insulin. Fasting led to a reduction in glucose metabolic rate in the myocardium (19.41 ± 5.39 vs. 3.26 ± 1.97 mg/min/100 g; p < 0.001), the skeletal muscle (1.06 ± 0.34 vs. 0.34 ± 0.08 mg/min/100 g; p = 0.001) but not the brain (3.21 ± 0.53 vs. 2.85 ± 0.25 mg/min/100 g; p = 0.19).ConclusionsChanges in organ SUVs, uptake rate constants and metabolic rates induced by fasting and insulin administration as observed in intact mice by small-animal PET imaging are consistent with those observed in isolated heart/muscle preparations and, more importantly, in vivo studies in larger animals and in humans. When assessing the effect of insulin on the myocardial glucose metabolism of non-fasted mice, it is not sufficient to just calculate the SUV - dynamic imaging with kinetic modeling is necessary.

Cold-induced expression of diapause in Praon volucre: fitness cost and morpho-physiological characterization

Cold exposure (2 degrees C for 7 days) in constant darkness at mummy stage induces diapause expression in 9% of the Praon volucre Haliday population. Diapausing parasitoids show a significant delay in emergence time compared with nondiapausing counterparts. A diapause-mediated polyphenism is observed in mummy colour, with diapausing mummies being clearly darker than nondiapausing ones. The diapause status of dark mummies is confirmed by a significant reduction in metabolic rate. Diapausing parasitoids also display specific morphological characteristics: they are heavier (fresh and dry mass) and accumulate larger fat reserves than nondiapausing counterparts. The diapause status is associated with a fitness cost in terms of adult longevity. There is no evidence of diapause-related change in supercooling ability.

The Brain Renin-Angiotensin System Controls Divergent Efferent Mechanisms to Regulate Fluid and Energy Balance

The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.

Erratum to: Coping with chaos: unpredictable food supplies intensify torpor use in an arid-zone marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata)

The severity, duration and amplitude of extreme weather events are forecast to intensify with current climate trends, over both long (e.g. seasonal) and short (e.g. daily) time-scales. As such, the predictability of food supplies for many small endotherms is likely to become increasingly important. Numerous small mammals and birds combat food shortages using torpor, a controlled reduction in metabolic rate and body temperature that helps lower their daily energy requirements. As such, torpor often has been cited as a key feature allowing some small endotherms to survive highly unpredictable climates, such as tropics or dry deserts, but mensurative demonstrations of this are lacking. We have shown here that when a small desert marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata), is offered unpredictable levels of daily food, they increase frequency of daily torpor and length of bouts compared with animals offered ad libitum food, but this was not found for animals offered a 70% food-restricted diet. Our data suggest that simple food restriction may not be sufficient for evaluating the efficacy of torpor as a strategy for managing unpredictable climates.

Brain Tissue Oxygenation During Dexmedetomidine Administration in Surgical Patients With Neurovascular Injuries

Investigations in dogs have shown substantial dexmedetomidine (Dex)-induced reductions in cerebral blood flow (CBF) unaccompanied by reductions in cerebral metabolic rate (CMR). If this effect were to occur in humans in areas of injured brain in which CBF is already low, oxygen delivery might be critically impaired. The institutional use of brain PO2 monitoring during neurovascular surgery and the use of Dex as a component of the anesthetic allowed insight into this issue. Data from 5 neurovascular surgery patients, 2 for excision of arteriovenous malformations (AVMs), and 3 for intracranial aneurysm clipping were reviewed retrospectively. All had acute, lesion-related neurologic deficits. During general anesthesia with sufentanil and sevoflurane, with or without N2O, a parenchymal brain tissue PO2 (PbrO2) electrode was placed directly in the territory at risk from the pending neurosurgical intervention. After a stable PbrO2 value was achieved, Dex was administered by bolus (1 μg/kg over 10 min) and infusion (0.5 to 0.7 μg/kg/min). Mean arterial pressure (MAP), heart rate (HR), and PbrO2 were observed continuously for at least 25 minutes. Baseline PbrO2 values were relatively low (≤16 mm Hg) in 4 of the 5 patients, a pattern consistent with antecedent neurologic insult. In the 15 minutes after initiation of Dex administration, the pattern was one of a modest increase in Pbr02 (maximum 11.1%; P=0.0147) occurring roughly in parallel with a modest increase in MAP [maximum 3.5 mm Hg (4.5%); P=0.041]. HR did not change. Clinically significant reduction of PbrO2 did not occur before neurosurgical interventions. These observations provide no support for a direct cerebral vasoconstrictive effect of Dex in humans that is independent of any vasoconstriction that may occur as a consequence of Dex-induced reduction in CMR. At a minimum, any such effect was insufficient to have an adverse effect on oxygen delivery to brain parenchyma.

Insulin Resistance and Alzheimer-like Reductions in Regional Cerebral Glucose Metabolism for Cognitively Normal Adults With Prediabetes or Early Type 2 Diabetes

Insulin resistance is a causal factor in prediabetes (PD) and type 2 diabetes (T2D) and increases the risk of developing Alzheimer disease (AD). Reductions in cerebral glucose metabolic rate (CMRglu) as measured by fludeoxyglucose F 18-positron emission tomography (FDG-PET) in parietotemporal, frontal, and cingulate cortices are associated with increased AD risk and can be observed years before dementia onset. To examine whether greater homeostasis model assessment insulin resistance (HOMA-IR) is associated with reduced resting CMRglu in areas vulnerable in AD in cognitively normal adults with newly diagnosed PD or T2D (PD/T2D), and to determine whether adults with PD/T2D have abnormal patterns of CMRglu during a memory encoding task. Randomized crossover design of resting and activation FDG-PET. University imaging center and Veterans Affairs clinical research unit. Twenty-three older adults (mean [SEM] age, 74.4 [1.4] years) with no prior diagnosis of diabetes but who met American Diabetes Association glycemic criteria for PD (n = 11) or diabetes (n = 12) based on fasting or 2-hour oral glucose tolerance test (OGTT) glucose values and 6 adults (mean [SEM] age, 74.3 [2.8] years) with normal fasting glucose values and glucose tolerance. No participant met Petersen criteria for mild cognitive impairment. Fasting participants underwent resting and cognitive activation FDG-PET imaging on separate days. Following a 30-minute transmission scan, subjects received an intravenous injection of 5 mCi of FDG, and the emission scan commenced 40 minutes after injection. In the activation condition, a 35-minute memory encoding task was initiated at the time of tracer injection. Subjects were instructed to remember a repeating list of 20 words randomly presented in series through earphones. Delayed free recall was assessed once the emission scan was complete. The HOMA-IR value was calculated using fasting glucose and insulin values obtained during OGTT screening and then correlated with CMRglu values obtained during the resting scan. Resting CMRglu values were also subtracted from CMRglu values obtained during the memory encoding activation scan to examine task-related patterns of CMRglu. Greater insulin resistance was associated with an AD-like pattern of reduced CMRglu in frontal, parietotemporal, and cingulate regions in adults with PD/T2D. The relationship between CMRglu and HOMA-IR was independent of age, 2-hour OGTT glucose concentration, or apolipoprotein E ε4 allele carriage. During the memory encoding task, healthy adults showed activation in right anterior and inferior prefrontal cortices, right inferior temporal cortex, and medial and posterior cingulate regions. Adults with PD/T2D showed a qualitatively different pattern during the memory encoding task, characterized by more diffuse and extensive activation, and recalled fewer items on the delayed memory test. Insulin resistance may be a marker of AD risk that is associated with reduced CMRglu and subtle cognitive impairments at the earliest stage of disease, even before the onset of mild cognitive impairment.

Anaerobic metabolic patterns related to stress responses in hypoxia exposed mussels Mytilus galloprovincialis

Air exposure in mussels during summer coincides with the concomitant exposure of the organism to hypoxia and ambient heat. The present study examined the metabolic and molecular stress responses of M. galloprovincialis during exposure to air at different temperatures. Mussel mortality did not rise upon 48 h of air exposure at 18° but increased significantly within the first 20 h of exposure to 32 °C. Thermal responses and limits were determined by integrating information from various levels of biological organization. Metabolic impacts were assessed by examining the activity of the key glycolytic enzyme pyruvate kinase (PK). Molecular responses were addressed through the expression of heat shock proteins Hsp70 and Hsp90 and the phosphorylation of stress-activated protein kinases, p38 mitogen-activated protein kinase (p38 MAPK) and cJun-N-terminal kinases (JNKs). PK activity decreased during exposure in a temperature dependent manner indicating a marked reduction of metabolic rate especially when M. galloprovincialis was exposed to 32 °C. The heat shock response (HSR) was stimulated in all cases of exposure indicating that hypoxia by itself may induce the expression of Hsp70 and Hsp90 in the tissues of M. galloprovincialis. Increased phosphorylation of p38 MAPK and JNKs indicate activation of MAPK signaling cascades. The potential involvement of MAPKs in the induction of Hsp genes in tissues of M. galloprovincialis during hypoxia is discussed.

One for all and all for one: the energetic benefits of huddling in endotherms

Huddling can be defined as "an active and close aggregation of animals". It is a cooperative group behaviour, permitting individuals involved in social thermoregulation to minimize heat loss and thereby lower their energy expenditure, and possibly allowing them to reallocate the saved energy to other functions such as growth or reproduction. Huddling is especially important in the case of animals faced with high heat loss due to a high surface-to-volume ratio, poor insulation, or living in cold environments. Although numerous experimental studies have focused on the huddling behaviour of a wide range of species, to our knowledge, this is the first attempt to review the various implications of this widely used behavioural strategy. Huddling allows individuals to maximise energy savings by (1) decreasing their cold-exposed body surface area, (2) reducing their heat loss through warming of ambient temperatures surrounding the group, and (3) eventually lowering their body temperature through physiological processes. Huddling provides substantial energy savings and is estimated to reduce energy expenditure by between 6 and 53%. Broad variations in the energetic benefits of huddling depend on the number of individuals and species involved in huddles, the ambient temperatures to which individuals are exposed and the density of the aggregations. It has been shown that huddling individuals have increased survival, a lower food intake, a decreased body mass loss, increased growth rate, reduced water loss, and/or a more constant body temperature together with a significant reduction in metabolic rate. Though huddling has been studied widely, this review reveals the intricacies of this adaptive behaviour.

Coping with chaos: unpredictable food supplies intensify torpor use in an arid-zone marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata)

The severity, duration and amplitude of extreme weather events are forecast to intensify with current climate trends, over both long (e.g. seasonal) and short (e.g. daily) time-scales. As such, the predictability of food supplies for many small endotherms is likely to become increasingly important. Numerous small mammals and birds combat food shortages using torpor, a controlled reduction in metabolic rate and body temperature that helps lower their daily energy requirements. As such, torpor often has been cited as a key feature allowing some small endotherms to survive highly unpredictable climates, such as tropics or dry deserts, but mensurative demonstrations of this are lacking. We have shown here that when a small desert marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata), is offered unpredictable levels of daily food, they increase frequency of daily torpor and length of bouts compared with animals offered ad libitum food, but this was not found for animals offered a 75% [corrected] food-restricted diet. Our data suggest that simple food restriction may not be sufficient for evaluating the efficacy of torpor as a strategy for managing unpredictable climates.

Blood Temperature Profiles of Diving Elephant Seals

Hypothermia-induced reductions in metabolic rate have been proposed to suppress metabolism and prolong the duration of aerobic metabolism during dives of marine mammals and birds. To determine whether core hypothermia might contribute to the repetitive long-duration dives of the northern elephant seal Mirounga angustirostris, blood temperature profiles were obtained in translocated juvenile elephant seals equipped with a thermistor and backpack recorder. Representative temperature (the y-intercept of the mean temperature vs. dive duration relationship) was 37.2 degrees C +/- 0.6 degrees C (n=3 seals) in the extradural vein, 38.1 degrees C +/- 0.7 degrees C (n = 4 seals) in the hepatic sinus, and 38.8 degrees +/- 1.6 degrees C (n = 6 deals) in the aorta. Mean temperature was significantly though weakly negatively related to dive duration in all but one seal. Mean venous temperatures of all dives of individual seals ranged between 36 degrees and 38 degrees C, while mean arterial temperatures ranged between 35 degrees and 39 degrees C. Transient decreases in venous and arterial temperatures to as low as 30 degrees -33 degrees C occurred in some dives >30 min (0.1% of dives in the study). The lack of significant core hypothermia during routine dives (10-30 min) and only a weak negative correlation of mean temperature with dive duration do not support the hypothesis that a cold-induced Q(10) effect contributes to metabolic suppression of central tissues during dives. The wide range of arterial temperatures while diving and the transient declines in temperature during long dives suggest that alterations in blood flow patterns and peripheral heat loss contribute to thermoregulation during diving.

Bioenergetics of torpor in the Microbiotherid marsupial, Monito del Monte (Dromiciops gliroides): the role of temperature and food availability

Torpor is the physiologically controlled reduction of metabolic rate and body temperature experienced by small birds and mammals when facing periods of low temperature and/or food shortage. In this study, we provide a first quantitative description of torpor in the relict marsupial Dromiciops gliroides by: (1) characterizing body temperature (T (B)) and torpor patterns, (2) evaluating the combined effects of ambient temperature and different levels of food restriction on torpor incidence and (3) exploring the metabolic depression during torpor. D. gliroides exhibited short bouts of torpor on a daily basis, during which T (B) decreased close to ambient temperature. During the active phase, T (B) also exhibited pronounced variation (range 34-38 degrees C). In order to evaluate the consistency of torpor, we computed the repeatability of T (B). Using the whole dataset, repeatability was significant (tau = 0.28). However, when torpid individuals were excluded from the analysis, repeatability was non-significant: some individuals were more prone to experience torpor than others. Our results indicate that this species also exhibits short bouts of daily torpor, whose depth and duration depends on the joint effects of T (A) and food availability. At T (A) = 20 degrees C, the maximum torpor incidence was found at 70-80% food reduction, while at both extremes of the food continuum (100 and 0-10% food reduction) individuals were completely active, although considerable variation in T (B) was recorded. At T (A) = 10 degrees C, individuals developed a deep form of torpor that was independent of the amount of food provided. On average, torpid D. gliroides reduced their metabolic rate up to 92% of their active values. In general, our results suggest that T (A) was the most immediate determinant of torpor, followed by energy availability.

Effects of Ghrelin Administration After Total Gastrectomy: A Prospective, Randomized, Placebo-Controlled Phase II Study

Body weight (BW) loss and reduction of blood ghrelin level are commonly observed after total gastrectomy (TG). A prospective study was designed to elucidate whether exogenous ghrelin administration prevents postoperative BW loss by improving appetite and oral food intake in patients with gastric cancer after undergoing TG. In this randomized phase II study, 21 patients undergoing TG were assigned to a ghrelin (11 patients) or placebo group (10 patients). They received intravenous infusion of synthetic human ghrelin (3 microg/kg) or saline twice daily for 10 days after starting oral food intake following surgery. Changes in BW, appetite visual analog scale score, food intake calories, body composition, basal metabolic rate, and various blood test results were evaluated. Excluding one patient who developed profound diaphoresis during ghrelin infusion, 20 patients completed the study. Food intake and appetite were significantly higher with ghrelin compared with placebo (average, 13.8 vs 10.4 kcal/kg/day [P = .030] and 5.7 vs 3.9 cm [P = .032], respectively). BW loss was significantly lower in the ghrelin than in the placebo group (-1.4% vs -3.7%; P = .044). Fat mass, lean body mass, and basal metabolic rate decreased significantly in the placebo group; however, the reductions in lean body mass and basal metabolic rate were not significant in the ghrelin group, although that of fat mass was significant. Short-term administration of synthetic ghrelin was safe and successfully lessened postoperative BW loss and improved appetite and food intake after TG.

An overview of stress response and hypometabolic strategies in Caenorhabditis elegans: conserved and contrasting signals with the mammalian system.

Studies of the molecular mechanisms that are involved in stress responses (environmental or physiological) have long been used to make links to disease states in humans. The nematode model organism, Caenorhabditis elegans, undergoes a state of hypometabolism called the 'dauer' stage. This period of developmental arrest is characterized by a significant reduction in metabolic rate, triggered by ambient temperature increase and restricted oxygen/ nutrients. C. elegans employs a number of signal transduction cascades in order to adapt to these unfavourable conditions and survive for long times with severely reduced energy production. The suppression of cellular metabolism, providing energetic homeostasis, is critical to the survival of nematodes through the dauer period. This transition displays molecular mechanisms that are fundamental to control of hypometabolism across the animal kingdom. In general, mammalian systems are highly inelastic to environmental stresses (such as extreme temperatures and low oxygen), however, there is a great deal of conservation between the signal transduction pathways of nematodes and mammals. Along with conserving many of the protein targets in the stress response, many of the critical regulatory mechanisms are maintained, and often differ only in their level of expression. Hence, the C. elegans model outlines a framework of critical molecular mechanisms that may be employed in the future as therapeutic targets for addressing disease states.

Hibernation and daily torpor in Australian mammals

Torpor is the most effective means for energy conservation available to mammals and is characterized by substantial reductions in body temperature (T b ) and metabolic rate (MR). Most Australian terrestrial mammals are small with high mass-specific energy requirements and, although it is widely believed that torpor is not needed in a ‘warm’ country like Australia, a large number of species are heterothermic (i.e. capable of changing T b , in contrast to homeothermic mammals with a constant high T b ). These heterothermic species (estimated >43% of terrestrial Australian native mammals) employ periods of daily torpor or prolonged multi-day torpor (hibernation) to conserve energy. Daily torpor is used by dasyurids (e.g. dunnarts, antechinus, quolls), myrmecobiids (numbat), tarsipedids (honey-possum), petaurid possums (e.g. sugar glider), rodents (but only known in the introduced house mouse), and small megabats (blossom-bats). During daily torpor, T b is reduced from ~35oC during the active or normothermic phase to ~10-25oC during torpor, and the torpor MR (TMR) is ~30% of the basal metabolic rate (BMR). Daily torpor is often, but not exclusively, used during the rest phase and, between bouts of torpor, animals usually forage and feed. Recent evidence shows that free-ranging arid zone dasyurids may employ daily torpor on every day in winter and that torpor may last twice as long as in captivity (often up to around 20 hours), which will reduce energy expenditure and thereby food requirements by up to 80%. Hibernation or prolonged torpor has been observed in the Monotremes (echidna), marsupials (pygmy-possums and feathertail glider) and insectivorous bats (e.g. long-eared bats). During prolonged torpor, which often, but not exclusively, is expressed in winter, T b is usually reduced to a minimum of ~0-10oC, and torpor bouts may last for several days or weeks, but in all species periodic arousals with brief normothermic periods (hours) between bouts of torpor have been observed. The TMR during hibernation is extremely low and can be as little as 1-5% of the BMR; daily energy expenditure can be reduced to only 3% of that in active individuals permitting survival on stored body fat for months without the need to feed. Daily and prolonged torpor in many Australian mammals appear to be opportunistic and not only important for survival of adverse seasonal conditions, but apparently also for dealing with unpredictable events such as droughts and perhaps fires and floods. As torpor substantially reduces energy requirements its use will in turn reduce the need for foraging and consequently exposure to predators. Predator avoidance by employing torpor and minimising foraging may be one of the reasons why none of the known heterothermic Australian species has gone extinct. In contrast many of the similar-sized perceived homeothermic species, such as rodents and bandicoots, have suffered high rates of extinction possibly because they must forage long and frequently to meet large energetic demands and thus are more vulnerable to predation by introduced foxes and cats.