Methods to estimate body temperature and energy expenditure dynamics in fed and fasted laboratory mice: effects of sleep deprivation and light exposure.

Monitoring body temperature and energy expenditure in freely-moving laboratory mice remains a powerful methodology used widely across a variety of disciplines-including circadian biology, sleep research, metabolic phenotyping, and the study of body temperature regulation. Some of the most pronounced changes in body temperature are observed when small heterothermic species reduce their body temperature during daily torpor. Daily torpor is an energy saving strategy characterized by dramatic reductions in body temperature employed by mice and other species when challenged to meet energetic demands.

Activation of oxytocinergic neurons enhances torpor in mice.

Mus musculus enters a torpid state in response to caloric restriction in sub-thermoneutral ambient temperatures. This torpid state is characterized by an adaptive and controlled decrease in metabolic rate, heart rate, body temperature, and activity. Previous research has identified the paraventricular nucleus (PVN) within the hypothalamus, a region containing oxytocin neurons, as a location that is active during torpor onset.

Health Effects of Alternate Day Fasting Versus Pair-Fed Caloric Restriction in Diet-Induced Obese C57Bl/6J Male Mice.

Alternate day fasting (ADF) induces weight loss and improves various markers of health in rodents and humans. However, it is unclear whether the benefits of ADF are derived from the lower caloric intake of ADF or from the 24-h fasting period. Therefore, this study directly compared selected markers for health - such as glucose control, body weight, liver triglycerides, T cell frequencies, and others - in high-fat (60% calories from fat) diet-induced obese mice subjected to either ADF or caloric restriction (CR).

Behavioral thermoregulation in the fasted C57BL/6 mouse.

Under relatively cool ambient temperatures and a caloric deficit, mice will undergo daily torpor - a short-term regulated reduction in metabolic rate with a concomitant drop in body temperature. Mice can alternatively achieve metabolic savings by utilizing behavioral changes, such as seeking a warmer environment. However, there is a lack of knowledge about the behavioral interaction between torpor utilization and thermotaxis.

Physiological response to the odorant TMT in fully fed and calorically restricted laboratory mice.

2,3,5-trimethyl-3-thiazoline (TMT) is a chemical compound that is extracted from red fox urine and can be used to artificially simulate the presence of a predator. The purpose of this study was to test the hypothesis that TMT would block entry into torpor in the calorically restricted C57Bl/6 mouse. We first demonstrated that TMT induced fear in the mouse.

The physiological signature of daily torpor is not orexin dependent.

Under conditions of scarce food availability and cool ambient temperature, the mouse (Mus Musculus) enters into torpor, a state of transient metabolic suppression mediated in part by the autonomic nervous system. Hypothalamic orexins are involved in the coordination of behaviors and autonomic function. We tested whether orexins are necessary for the coordinated changes in physiological variables, which underlie torpor and represent its physiological signature.

Effect of stevia on the gut microbiota and glucose tolerance in a murine model of diet-induced obesity.

Artificial sweeteners have been shown to induce glucose intolerance by altering the gut microbiota; however, little is known about the effect of stevia. Here, we investigate whether stevia supplementation induces glucose intolerance by altering the gut microbiota in mice, hypothesizing that stevia would correct high fat diet-induced glucose intolerance and alter the gut microbiota. Mice were split into four treatment groups: low fat, high fat, high fat + saccharin and high fat + stevia.

A robust diving response in the laboratory mouse.

The diving response is a coordinated physiological response to submersion under water and has been documented amongst all mammals tested to date. The physiological response consists of three primary reflexes: an immediate bradycardia, apnea, and selective constriction of peripheral blood vessels. We hypothesized that mice would exhibit a diving response upon voluntary submersion into water typically seen in other mammals.

Alternate-day feeding leads to improved glucose regulation on fasting days without significant weight loss in genetically obese mice.

Alternate-day fasting (ADF) is effective for weight loss and increases insulin sensitivity in diet-induced obese rodents. However, the efficacy of ADF in genetic models of obesity has not been comprehensively studied. Mice that are deficient in leptin ( mice) are obese, diabetic, and prone to deep bouts of torpor when fasted.

The impact of deep breathing and alternate nostril breathing on heart rate variability: a human physiology laboratory.

An increase in the beat-to-beat variability of heart rate (HRV) is a robust marker of enhanced parasympathetic activity and of a calm and relaxed state. The purpose of this laboratory activity was to introduce the concept of HRV to our students, while having them address a novel question of whether two yogic breathing techniques, namely alternate nostril breathing (ANB) and standard deep breathing (DB), impact the SD of instantaneous heart rate (SDHR), a measure of HRV. Fifty-five undergraduates enrolled in a physiology course designed for nonscience majors were tasked with analyzing HR and SDHR from electrocardiograms recorded during normal breathing, DB, and ANB.

The heat is on: A device that reduces cold stress-induced tachycardia in laboratory mice.

Mouse vivaria are typically maintained at an ambient temperature (T) of 20-26 °C which is comfortable for human researchers. However, as this T is well below the mouse thermoneutral zone (TNZ) of 30-32 °C, typical vivarium temperatures result in cold stress for mice. Recently, a cage has been developed that provides variable cage floor heating, allowing mice to behaviorally regulate body temperature through thermotaxis.

Neurons in ventral tegmental area tonically inhibit sympathetic outflow to brown adipose tissue: possible mediation of thermogenic signals from lateral habenula.

The lateral habenula (LHb), a nucleus involved in the response to salient, especially adverse, environmental events, is implicated in brown adipose tissue (BAT) thermogenesis caused by these events. LHb-elicited thermogenesis involves a neural pathway to the lower brain stem sympathetic control center in the medullary raphé. There are no direct connections from the LHb to the medullary raphé.

Changes in blood glucose as a function of body temperature in laboratory mice: implications for daily torpor.

Many small mammals, such as the laboratory mouse, utilize the hypometabolic state of torpor in response to caloric restriction. The signals that relay the lack of fuel to initiate a bout of torpor are not known. Because the mouse will only enter a torpid state when calorically challenged, it may be that one of the inputs for initiation into a bout of torpor is the lack of the primary fuel (glucose) used to power brain metabolism in the mouse.

Defective daily temperature regulation in a mouse model of amyotrophic lateral sclerosis.

Current understanding of the pathogenesis of the familial form of amyotrophic lateral sclerosis has been aided by the study of transgenic mice that over-express mutated forms of the human CuZn-superoxide dismutase (SOD1) gene. While mutant SOD1 in motor neurons determines disease onset, other non-cell autonomous factors are critical for disease progression, and altered energy metabolism has been implicated as a contributing factor. Since most energy expended by laboratory mice is utilized to defend body temperature (T), we analyzed thermoregulation in transgenic mice carrying the G93A mutation of the human SOD1 gene, using implantable temperature data loggers to continuously record T for up to 85 days.

Clocks and meals keep mice from being cool.

Daily torpor is used by small mammals to reduce daily energy expenditure in response to energetic challenges. Optimizing the timing of daily torpor allows mammals to maximize its energetic benefits and, accordingly, torpor typically occurs in the late night and early morning in most species. However, the regulatory mechanisms underlying such temporal regulation have not been elucidated.

Is Adenosine Action Common Ground for NREM Sleep, Torpor, and Other Hypometabolic States?

This review compares two states that lower energy expenditure: non-rapid eye movement (NREM) sleep and torpor. Knowledge on mechanisms common to these states, and particularly on the role of adenosine in NREM sleep, may ultimately open the possibility of inducing a synthetic torpor-like state in humans for medical applications and long-term space travel. To achieve this goal, it will be important, in perspective, to extend the study to other hypometabolic states, which, unlike torpor, can also be experienced by humans.

Desynchrony between brain and peripheral clocks caused by CK1δ/ε disruption in GABA neurons does not lead to adverse metabolic outcomes.

Circadian disruption as a result of shift work is associated with adverse metabolic consequences. Internal desynchrony between the phase of the suprachiasmatic nuclei (SCN) and peripheral clocks is widely believed to be a major factor contributing to these adverse consequences, but this hypothesis has never been tested directly. A GABAergic Cre driver combined with conditional casein kinase mutations ( ) was used to lengthen the endogenous circadian period in GABAergic neurons, including the SCN, but not in peripheral tissues, to create a Discordant mouse model.

Heart rate dynamics in a marsupial hibernator.

The eastern pygmy possum () is a small marsupial that can express spontaneous short bouts of torpor, as well as multi-day bouts of deep hibernation. To examine heart rate () control at various stages of torpor in a marsupial hibernator, and to see whether variability differs from that of deep placental hibernators, we used radiotelemetry to measure ECG and body temperature () while measuring the rate of O consumption and ventilation. and O consumption rate during euthermia were at a minimum (321±34 beats min, 0.

Central activation of the A adenosine receptor in fed mice recapitulates only some of the attributes of daily torpor.

Mice enter bouts of daily torpor, drastically reducing metabolic rate, core body temperature (T ), and heart rate (HR), in response to reduced caloric intake. Because central adenosine activation has been shown to induce a torpor-like state in the arctic ground squirrel, and blocking the adenosine-1 (A) receptor prevents daily torpor, we hypothesized that central activation of the A adenosine receptors would induce a bout of natural torpor in mice. To test the hypothesis, mice were subjected to four different hypothermia bouts: natural torpor, forced hypothermia (FH), isoflurane-anesthesia, and an intracerebroventricular injection of the selective A receptor agonist Ncyclohexyladenosine (CHA).

Accurate discrimination of the wake-sleep states of mice using non-invasive whole-body plethysmography.

A major limitation in the study of sleep breathing disorders in mouse models of pathology is the need to combine whole-body plethysmography (WBP) to measure respiration with electroencephalography/electromyography (EEG/EMG) to discriminate wake-sleep states. However, murine wake-sleep states may be discriminated from breathing and body movements registered by the WBP signal alone. Our goal was to compare the EEG/EMG-based and the WBP-based scoring of wake-sleep states of mice, and provide formal guidelines for the latter.

Group housing and nest building only slightly ameliorate the cold stress of typical housing in female C57BL/6J mice.

Huddling and nest building are two methods of behavioral thermoregulation used by mice under cold stress. In the laboratory, mice are typically housed at an ambient temperature (Ta) of 20°C, well below the lower end of their thermoneutral zone. We tested the hypothesis that the thermoregulatory benefits of huddling and nest building at a Ta of 20°C would ameliorate this cold stress compared with being singly housed at 20°C as assessed by heart rate (HR), blood pressure (BP), triiodothyronine (T3), brown adipose (BAT) expression of Elovl3 mRNA, and BAT lipid content.

Three months of high-fructose feeding fails to induce excessive weight gain or leptin resistance in mice.

High-fructose diets have been implicated in obesity via impairment of leptin signaling in humans and rodents. We investigated whether fructose-induced leptin resistance in mice could be used to study the metabolic consequences of fructose consumption in humans, particularly in children and adolescents. Male C57Bl/6 mice were weaned to a randomly assigned diet: high fructose, high sucrose, high fat, or control (sugar-free, low-fat).

Chronic rapamycin treatment causes diabetes in male mice.

Current evidence indicates that the mammalian target of rapamycin inhibitor rapamycin both increases longevity and, seemingly contradictorily, impairs glucose homeostasis. Most studies exploring the dimensions of this paradox have been based on rapamycin treatment in mice for up to 20 wk. We sought to better understand the metabolic effects of oral rapamycin over a substantially longer period of time in HET3 mice.

Oxyntomodulin increases intrinsic heart rate through the glucagon receptor.

Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM), vigorously elevate the intrinsic heart rate (IHR) of mice. We have previously shown that OXM influences murine heart rate (HR) independent of the glucagon-like peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice deficient in the glucagon receptor (Gcgr -/-) that both OXM and glucagon require the glucagon receptor for their chronotropic effects on the heart.