Elevated Core Body Temperature Research Articles

Knockdown of NPY Expression in the Dorsomedial Hypothalamus Promotes Development of Brown Adipocytes and Prevents Diet-Induced Obesity

Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympathetic nervous system. This knockdown increased uncoupling protein 1 expression in both inguinal fat and interscapular brown adipose tissue (BAT). Consistent with the activation of BAT, DMH NPY knockdown increased energy expenditure and enhanced the thermogenic response to a cold environment. This knockdown also increased locomotor activity, improved glucose homeostasis, and enhanced insulin sensitivity. Together, these results demonstrate critical roles of DMH NPY in body weight regulation through affecting food intake, body adiposity, thermogenesis, energy expenditure, and physical activity.

Season of birth in schizophrenia: A maternal–fetal chronobiological hypothesis

Being born in the winter and spring significantly increases one’s risk for developing schizophrenia. This birth seasonality may account for as many as 10% of all cases of schizophrenia. Maternal third trimester infections or vitamin D deficiencies are hypothesized to be the most likely cause and can account for many of the important features of schizophrenia, although each hypothesis has limitations. Alternatively, around the winter solstice, reduced maternal sunlight exposure during the second trimester of pregnancy may result in a reduced amplitude maternal circadian pacemaker, reduced maternal nocturnal plasma melatonin concentrations, elevated maternal nocturnal core body and incubator temperatures, and elevated fetal core body and brain temperatures. Indeed, studies in humans have shown that the core body temperatures of human fetuses near birth may vary by >2.5 °C. Reduced melatonin concentrations and elevated temperatures have been shown to have detrimental effects on immature hippocampal neurons in animals. In addition, plasma melatonin concentrations and core body temperatures are critical determinants of the dopaminergic programming of the striatal component of the human central thermostat, which appears to be functioning by the second trimester of gestation and responsive to whatever chronobiological signals its mother correctly or incorrectly transduces from the prevailing meteorological conditions. Both hippocampal and striatal thermostat dysfunction may result in reduced striatal extracellular dopamine concentrations and a tendency towards increased phasic dopamine release—the characteristic biochemical lesion in schizophrenia. Thus, the maternal–fetal chronobiological dysfunction hypothesis could account for the birth seasonality in schizophrenia and warrants further investigation.

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.

Acute starvation alters lipopolysaccharide-induced fever in leptin-dependent and -independent mechanisms in rats

A decrease in leptin levels with the onset of starvation triggers a myriad of physiological responses including immunosuppression and hypometabolism/hypothermia, both of which can counteract the fever response to pathogens. Here we examined the role of leptin in LPS-induced fever in rats that were fasted for 48 h prior to inflammation with or without leptin replacement (12 μg/day). The preinflammation fasting alone caused a progressive hypothermia that was almost completely reversed by leptin replacement. The LPS (100 μg/kg)-induced elevation in core body temperature (T(core)) was attenuated in the fasted animals at 2-6 h after the injection, an effect that was not reversed by leptin replacement. Increasing the LPS dose to 1,000 μg/kg caused a long-lasting fever that remained unabated for up to 36 h after the injection in the fed rats. This sustained response was strongly attenuated in the fasted rats whose T(core) started to decrease by 18 h after the injection. Leptin replacement almost completely restored the prolonged fever. The attenuation of the prolonged fever in the fasted animals was accompanied by the diminution of proinflammatory PGE(2) in the cerebrospinal fluid and mRNA of proopiomelanocortin (POMC) in the hypothalamus. Leptin replacement prevented the fasting-induced reduction of POMC but not PGE(2). Moreover, the leptin-dependent fever maintenance correlated closely with hypothalamic POMC levels (r = 0.77, P < 0.001). These results suggest that reduced leptin levels during starvation attenuate the sustained fever response by lowering hypothalamic POMC tone but not PGE(2) synthesis.

Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2and diet‐induced obesity

Decrease in fat catabolic rate on consuming a high-fat diet contributes to diet-induced obesity. This study used group 1B phospholipase A(2) (Pla2g1b)-deficient mice, which are resistant to hyperglycemia, to test the hypothesis that Pla2g1b and its lipolytic product lysophospholipid suppress hepatic fat utilization and energy metabolism in promoting diet-induced obesity. The metabolic consequences of hypercaloric diet, including body weight gain, energy expenditure, and fatty acid oxidation, were compared between Pla2g1b(+/+) and Pla2g1b(-/-) mice. The Pla2g1b(-/-) mice displayed normal energy balance when fed chow, but were resistant to obesity when challenged with a hypercaloric diet. Obesity resistance in Pla2g1b(-/-) mice is due to their ability to maintain elevated energy expenditure and core body temperature when subjected to hypercaloric diet, which was not observed in Pla2g1b(+/+) mice. The Pla2g1b(-/-) mice also displayed increased postprandial hepatic fat utilization due to increased expression of peroxisome proliferator-activated receptor (PPAR)-alpha, PPAR-delta, PPAR-gamma, cd36/Fat, and Ucp2, which coincided with reduced postprandial plasma lysophospholipid levels. Lysophospholipids produced by Pla2g1b hydrolysis suppress hepatic fat utilization and down-regulate energy expenditure, thereby preventing metabolically beneficial adaptation to a high-fat diet exposure in promoting diet-induced obesity and type 2 diabetes.

Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions

The current study, in parallel experiments, evaluated the impact of chronic psychological stress on physiological and behavioural measures, and on the activation status of microglia in 15 stress-responsive brain regions. Rats were subjected, for 14 days, to two 30 min sessions of restraint per day, applied at random times each day. In one experiment the effects of stress on sucrose preference, weight gain, core body temperature, and struggling behaviour during restraint, were determined. In the second experiment we used immunohistochemistry to investigate stress-induced changes in ionized calcium-binding adaptor molecule-1 (Iba1), a marker constitutively expressed by microglia, and major histocompatibility complex-II (MHC-II), a marker often expressed on activated microglia, in a total of 15 stress-responsive nuclei. We also investigated cellular proliferation in these regions using Ki67 immunolabelling, to check for the possibility of microglial proliferation. Collectively, the results we obtained showed that chronic stress induced a significant increase in anhedonia, a decrease in weight gain across the entire observation period, a significant elevation in core body temperature during restraint, and a progressive decrease in struggling behaviour within and over sessions. With regard to microglial activation, chronic stress induced a significant increase in the density of Iba1 immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight of 15 regions). Within the regions that exhibited an increased number of Iba1-positive cells after chronic stress, we found no evidence of a between group difference in the number of MHC-II or Ki67 positive cells. In summary, these results clearly demonstrate that chronic stress selectively increases the number of microglia in certain stress-sensitive brain regions, and also causes a marked transition of microglia from a ramified-resting state to a non-resting state. These findings are consistent with the view that microglial activation could play an important role in controlling and/or adapting to stress.

Aerobic Performance Is Degraded, Despite Modest Hyperthermia, in Hot Environments

Environmental heat stress degrades aerobic performance; however, little research has focused on performance when the selected task elicits modest elevations in core body temperature (<38.5 degrees C). To determine the effect of environmental heat stress, with modest hyperthermia, on aerobic performance and pacing strategies. After a 30-min cycling preload at 50% VO2peak, eight euhydrated men performed a 15-min time trial on a cycle ergometer in temperate (TEMP; 21 degrees C, 50% RH) and hot (HOT; 40 degrees C, 25% RH) environments. Core and skin temperature (Tc and Tsk, respectively) and HR were continuously monitored. Performance was assessed by the total work (kJ) completed in 15 min. Pacing was quantified by comparing the percent difference in actual work performed in each of five 3-min blocks normalized to the mean work performed per 3-min block. Pace over the final 2 min was compared with the average pace from minutes 0 to 13 for end spurt analysis. Tc and HR rose continually throughout both time trials. Peak Tc remained modestly elevated in both environments [mean (range): HOT = 38.20 degrees C (37.97-38.42 degrees C); TEMP = 38.11 degrees C (38.07-38.24 degrees C)], whereas Tsk was higher in HOT (36.19 +/- 0.40 degrees C vs 31.14 +/- 1.14 degrees C), and final HR reached approximately 95% of age-predicted maximum in both environments. Total work performed in HOT (147.7 +/- 23.9 kJ) was approximately 17% less (P < 0.05) than TEMP (177.0 +/- 25.0 kJ). Pace was evenly maintained in TEMP, but in HOT, volunteers were unable to maintain initial pace, slowing progressively over time. A significant end spurt was produced in both environments. During a brief aerobic exercise time trial where excessive hyperthermia is avoided, total work is significantly reduced by heat stress because of a gradual slowing of pace over time. These findings demonstrate how aerobic exercise performance degrades in hot environments without marked hyperthermia.

Ontogenetic changes in tracheal structure facilitate deep dives and cold water foraging in adult leatherback sea turtles

Adult leatherbacks are large animals (300-500 kg), overlapping in size with marine pinniped and cetacean species. Unlike marine mammals, they start their aquatic life as 40-50 g hatchlings, so undergo a 10,000-fold increase in body mass during independent existence. Hatchlings are limited to the tropics and near-surface water. Adults, obligate predators on gelatinous plankton, encounter cold water at depth (<1280 m) or high latitude and are gigantotherms that maintain elevated core body temperatures in cold water. This study shows that there are great ontogenetic changes in tracheal structure related to diving and exposure to cold. Hatchling leatherbacks have a conventional reptilian tracheal structure with circular cartilaginous rings interspersed with extensive connective tissue. The adult trachea is an almost continuous ellipsoidal cartilaginous tube composed of interlocking plates, and will collapse easily in the upper part of the water column during dives, thus avoiding pressure-related structural and physiological problems. It is lined with an extensive, dense erectile vascular plexus that will warm and humidify cold inspired air and possibly retain heat on expiration. A sub-luminal lymphatic plexus is also present. Mammals and birds have independently evolved nasal turbinates to fulfil such a respiratory thermocontrol function; for them, turbinates are regarded as diagnostic of endothermy. This is the first demonstration of a turbinate equivalent in a living reptile.

Elevated Body Core Temperature in Medico-Legal Investigation of Violent Death

Pathologically elevated body core temperature, measured at the death scene, is an important finding in medico-legal investigation of violent deaths. An abnormally high rectal temperature at any death scene may point to an underlying pathology, the influence of certain drugs or a hidden cerebral traumatism, and death by suffocation which would remain undetected without further medico-legal investigations. Furthermore, hyperthermia and fever, if unrecognized, may result in an erroneous forensic estimation of time since death in the early postmortem period by the "Henssge method." By a retrospective study of 744 cases, the authors demonstrate that hyperthermia is a finding with an incidence of 10% of all cases of violent death. The main causes are: influence of drugs, malignant tumors, cerebral hypoxia as a result of suffocation, infections, and systemic inflammatory disorders. As a consequence it must be stated, that hyperthermia must be excluded in every medico-legal death scene investigation by a correct measurement of body core temperature and a comparison between the cooling rate of the body and the behavior of early postmortem changes, notably livor and rigor mortis.

Temperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy

Heterozygous loss-of-function mutations in the alpha subunit of the type I voltage-gated sodium channel Na(V)1.1 cause severe myoclonic epilepsy in infancy (SMEI), an infantile-onset epileptic encephalopathy characterized by normal development followed by treatment-refractory febrile and afebrile seizures and psychomotor decline. Mice with SMEI (mSMEI), created by heterozygous deletion of Na(V)1.1 channels, develop seizures and ataxia. Here we investigated the temperature and age dependence of seizures and interictal epileptiform spike-and-wave activity in mSMEI. Combined video-EEG monitoring demonstrated that mSMEI had seizures induced by elevated body core temperature but wild-type mice were unaffected. In the 3 age groups tested, no postnatal day (P)17-18 mSMEI had temperature-induced seizures, but nearly all P20-22 and P30-46 mSMEI had myoclonic seizures followed by generalized seizures caused by elevated core body temperature. Spontaneous seizures were only observed in mice older than P32, suggesting that mSMEI become susceptible to temperature-induced seizures before spontaneous seizures. Interictal spike activity was seen at normal body temperature in most P30-46 mSMEI but not in P20-22 or P17-18 mSMEI, indicating that interictal epileptic activity correlates with seizure susceptibility. Most P20-22 mSMEI had interictal spike activity with elevated body temperature. Our results define a critical developmental transition for susceptibility to seizures in SMEI, demonstrate that body temperature elevation alone is sufficient to induce seizures, and reveal a close correspondence between human and mouse SMEI in the striking temperature and age dependence of seizure frequency and severity and in the temperature dependence and frequency of interictal epileptiform spike activity.

Characterization of the sickness response in young and aging rats following E. coli infection

To more fully characterize the sickness response in young (3 mo) and older (24 mo) rats, we measured core body temperature (CBT), activity level, and body weight changes for 7 days following a peripheral immune challenge with Escherichia coli. CBT increases were delayed and blunted during the 12 h following infection in older rats. Indeed, in aging subjects the initial response was hypothermia, but this was followed by a significant and prolonged elevation in CBT lasting 3 days. Young rats, in contrast, generated a rapid and robust CBT elevation lasting just over a day. Activity level was significantly reduced only on the day of E. coli administration in both young and older rats. Body weight loss was equivalent in both age groups one day after E. coli administration, although there was a trend for older rats to continue losing more weight across the next 6 days than in young rats. This is the first study to examine CBTs in young and older rats for a protracted amount of time, thereby revealing that aging rats do have an exaggerated, albeit delayed, fever which is in keeping with other exaggerated sickness behavioral responses observed in aging rodents.

Heat Stroke: Increased Signal Intensity in the Bilateral Cerebellar Dentate Nuclei and Splenium on Diffusion-Weighted MR Imaging: Fig 1.

Heat stroke is a critical illness characterized by hyperthermia (elevated core body temperature >40°C) with accompanying life-threatening complications. Previous MR imaging findings of heat stroke included diffuse atrophy of the cerebellum[1][1]; hyperintense lesions in the cerebellum,[1][1]–[3][

Impact of evaporative pads and cross ventilation on core body temperature and resting time of lactating cows (2009)

A trial was conducted to determine the impact of evaporative cooling pads on core body temperature (CBT), time spent lying, and number of lying bouts of Holstein cows housed in cross-ventilated freestall facilities. Despite cool ambient conditions during the trial, cows without evaporative pads tended to have elevated CBT above 102°F for 2.3 more hours per day and elevated CBT above 102.5°F for 0.95 more hours per day than cows with evaporative pads. These trends were evident even though the stocking density of the freestalls was greater in the facility with evaporative pads than in the facility without pads (123 vs. 113%). Lying times and lying bouts did not differ between treatments. Results of this study indicate that CBT tended to be reduced when evaporative pads were used, even under relatively mild ambient conditions.

Acid sensing ion channel (ASIC) inhibitors exhibit anxiolytic-like activity in preclinical pharmacological models

Acid sensing ion channels (ASICs) are proton-gated ion channels located in the central and peripheral nervous systems. Of particular interest is ASIC1a, which is located in areas associated with fear and anxiety behaviors. Recent reports suggest a role for ASIC1a in preclinical models of fear conditioning and anxiety. The present experiments evaluated various ASIC inhibitors in preclinical models of autonomic and behavioral parameters of anxiety. In addition, neurochemical studies evaluated the effects of an ASIC inhibitor (A-317567) on neurotransmitter levels in the amygdala. In electrophysiological studies using hippocampal primary neuronal cultures, three ASIC inhibitors (PcTX-1, A-317567, and amiloride) produced concentration-dependent inhibition of acid-evoked currents. In the stress-induced hyperthermia model, acute administration of psalmotoxin 1 (PcTX-1; 10-56 ng, i.c.v.), A-317567 (0.1-1.0 mg/kg, i.p.), and amiloride (10-100 mg/kg, i.p.) prevented stress-induced elevations in core body temperature. In the four-plate test, acute treatment with PcTX-1 (10-56 ng, i.c.v.) and A-317567 (0.01-0.1 mg/kg, i.p.), but not amiloride (3-100 mg/kg, i.p.), produced dose-dependent and significant increases in the number of punished crossings relative to vehicle-treated animals. Additionally, PcTX-1 (56-178 ng, i.c.v.), A-317567 (0.1-10 mg/kg, i.p.), and amiloride (10-100 mg/kg, i.p.) lacked significant anxiolytic-like activity in the elevated zero maze. In neurochemical studies, an infusion of A-317567 (100 microM) into the amygdala significantly elevated the extracellular levels of GABA, but not glutamate, in this brain region. These findings demonstrate that ASIC inhibition produces anxiolytic-like effects in some behavioral models and indicate a potential role for GABAergic mechanisms to underlie these anxiolytic-like effects.

Role of the hypothalamic PVN in the reflex reduction in mesenteric blood flow elicited by hyperthermia

The hypothalamic paraventricular nucleus (PVN) is an important integrative center in the brain. In the present study, we investigated whether the PVN is a key region in the mesenteric vasoconstriction that normally accompanies an increase in core body temperature. Anesthetized rats were monitored for blood pressure, heart rate, mesenteric blood flow, and vascular conductance. In control rats, elevation of core body temperature to 41 degrees C had no significant effect on blood pressure, increased heart rate, and reduced mesenteric blood flow by 21%. In a separate group of rats, muscimol was microinjected bilaterally (1 nmol/side) into the PVN. Compared with the control group, there was no significant difference in the blood pressure and heart rate responses elicited by the increase in core body temperature. In contrast to control animals, however, mesenteric blood flow did not fall in the muscimol-treated rats in response to the elevation in core body temperature. In a separate group, in which muscimol was microinjected into regions outside the PVN, elevating core body temperature elicited the normal reduction in mesenteric blood flow. The results suggest that the PVN may play a key role in the reflex decrease in mesenteric blood flow elicited by hyperthermia.

The relationship between insomnia and body temperatures

Sleepiness and sleep propensity are strongly influenced by our circadian clock as indicated by many circadian rhythms, most commonly by that of core body temperature. Sleep is most conducive in the temperature minimum phase, but is inhibited in a "wake maintenance zone" before the minimum phase, and is disrupted in a zone following that phase. Different types of insomnia symptoms have been associated with abnormalities of the body temperature rhythm. Sleep onset insomnia is associated with a delayed temperature rhythm presumably, at least partly, because sleep is attempted during a delayed evening wake maintenance zone. Morning bright light has been used to phase advance circadian rhythms and successfully treat sleep onset insomnia. Conversely, early morning awakening insomnia has been associated with a phase advanced temperature rhythm and has been successfully treated with the phase delaying effects of evening bright light. Sleep maintenance insomnia has been associated not with a circadian rhythm timing abnormality, but with nocturnally elevated core body temperature. Combination of sleep onset and maintenance insomnia has been associated with a 24-h elevation of core body temperature supporting the chronic hyper-arousal model of insomnia. The possibility that these last two types of insomnia may be related to impaired thermoregulation, particularly a reduced ability to dissipate body heat from distal skin areas, has not been consistently supported in laboratory studies. Further studies of thermoregulation are needed in the typical home environment in which the insomnia is most evident.

Post-Landing Orion Crew Survival in Warm Ocean Areas: A Case Study in Iterative Environmental Design

The Orion crew module (CM) is being designed to perform survivable land and water landings. There are many issues associated with post-landing crew survival. In general, the most challenging of the realistic Orion landing scenarios from an environmental control standpoint is the off-nominal water landing. Available power and other consumables will be very limited after landing, and it may not be possible to provide full environmental control within the crew cabin for very long after splashdown. Given the bulk and thermal insulation characteristics of the crew-worn pressure suits, landing in a warm tropical ocean area would pose a risk to crew survival from elevated core body temperatures, if for some reason the crewmembers were not able to remove their suits and/or exit the vehicle. This paper summarizes the analyses performed and conclusions reached regarding post-landing crew survival following a water landing, from the standpoint of the crew s core body temperatures.

Cooling Core Body Temperature May Slow Down Neurodegeneration

Reduction of core body temperature has been proposed to contribute to the increased lifespan and the anti-aging effects conferred by caloric restriction in mice and higher primates. Cooler biologically compatible core body temperatures have also been hypothesized to combat neurodegenerative disorders. Yet, validation of these hypotheses has been difficult until recently, when it demonstrated that transgenic mice engineered to have chronic low core body temperature have longer lifespan independent of alteration in diet or caloric restriction. This article reviews the literature and highlights the potential influence of core body temperature's governing role on aging and in the pathophysiology of neurodegenerative disorders in humans. What makes recent findings more significant for humans is the existence of several methods to lower and maintain low core body temperatures in human subjects. The therapeutic potential of "cooler people" may also raise the possibility that this could reverse the adverse-health consequences of elevations in core body temperature.

The effect of passive heating and head cooling on perception, cardiovascular function and cognitive performance in the heat

The present study examined the effects of raising both skin temperature and core temperature, separately and in combination, on perceptions of heat-related fatigue (alertness, contentment, calmness and thermal comfort), cardiovascular function and on objective measures of cognitive performance (reaction time and accuracy). Ten (six males) subjects had cognitive performance assessed in three conditions; at low skin and low core temperature (LL), at high skin and low core temperature (HL) and at high skin and high core temperatures (HH). In one trial, subjects had their head and neck cooled (HC); the other trial was a control (CON). Raising skin temperature increased heart rate and decreased perception of thermal comfort (P < 0.05), whereas raising both skin and core temperature decreased perception of heat-related fatigue (P < 0.05) and increased cardiovascular strain (P < 0.05) resulting in decrements in cognitive performance shown by faster reaction times (P < 0.05) and a loss of accuracy (P < 0.05). At high skin and core temperatures, cooling the head and neck improved feelings of heat-related fatigue (P < 0.05) and cardiovascular strain (P < 0.05), but had no effect on cognitive performance. In conclusion, the results of this study suggest that feelings of heat-related fatigue and cardiovascular strain can be attributed to a combination of elevated skin and core body temperature, whereas decrements in cognitive performance can be attributed to an elevated core temperature.

Enhancement of Myofibrillar Proteolysis Following Infusion of Amino Acid Mixture Correlates Positively with Elevation of Core Body Temperature in Rats

Administration of an amino acid (AA) mixture stimulates muscle protein synthesis and elevates core body temperature (T(b)), as characteristically found under anesthetic conditions. We tested the hypothesis that not only AA given, but also AA produced by degradation of endogenous muscular protein are provided for muscle protein synthesis, which is further reflected in T(b) modifications. Rats were intravenously administered an AA mixture or saline in combination with the anesthetic propofol or lipid emulsion. We measured plasma 3-methylhistidine (MeHis) concentrations as an index of myofibrillar protein degradation, rectal temperature and mRNA expression of atrogin-1, MuRF-1 and ubiquitin in gastrocnemius and soleus muscles of rats following 3 h infusion of test solutions. T(b) did not differ significantly between conscious groups, but was higher in the AA group than in the saline group among anesthetized rats. Plasma MeHis concentrations were higher in the AA group than in the saline group under both conditions. Plasma MeHis levels correlated positively with T(b) of rats under both conditions. AA administration decreased mRNA levels of atrogin-1 and ubiquitin in gastrocnemius muscle and all mRNA levels in soleus muscle. These results suggest that AA administration enhances myofibrillar protein degradation and that the change is a determinant of T(b) modification by AA administration. However, the mechanisms underlying AA administration-associated enhancement of myofibrillar proteolysis remains yet to be determined.