Showing papers in "American Journal of Physiology-regulatory Integrative and Comparative Physiology in 2007"
TL;DR: Mechanisms of in vivo ROS generation are described, the potential impact of ROS and oxidative damage on cellular function is examined, and how these responses change with aging in physiologically relevant situations are evaluated.
Abstract: Aging is an inherently complex process that is manifested within an organism at genetic, molecular, cellular, organ, and system levels. Although the fundamental mechanisms are still poorly understo...
829 citations
TL;DR: This review discusses the recent progress in the following areas: central and peripheral thermosensitivity and temperature-activated transient receptor potential (TRP) channels; afferent neuronal pathways from peripheral thermmosensors; and efferent thermoeffector pathways.
Abstract: While summarizing the current understanding of how body temperature (Tb) is regulated, this review discusses the recent progress in the following areas: central and peripheral thermosensitivity and...
626 citations
TL;DR: In summary, endurance exercise training increased IMCL area density due to an increase in the number of lipid droplets, whereas the increase in total mitochondrial area was due to a increases in the size of individual mitochondrial fragments.
Abstract: Impaired mitochondrial function and structure and intramyocellular lipid (IMCL) accumulation have been associated with obesity and Type 2 diabetes. We examined whether endurance exercise training and sex influenced IMCL and mitochondrial morphology using electron microscopy, whole-body substrate use, and mitochondrial enzyme activity. Untrained men (n = 5) and women (n = 7) were tested before and after 7 wk of endurance exercise training. Testing included 90 min of cycle ergometry at 60% Vo(2 peak) with preexercise muscle biopsies analyzed for IMCL and mitochondrial size/area using electron microscopy and short-chain beta-hydroxyacyl-CoA dehydrogenase (SCHAD) and citrate synthase (CS) enzyme activity. Training increased the mean lipid area density (P = 0.090), the number of IMCL droplets (P = 0.055), the number of IMCL droplets in contact with mitochondria (P = 0.010), the total mitochondrial area (P < 0.001), and the size of individual mitochondrial fragments (P = 0.006). Women had higher mean lipid area density (P = 0.030) and number of IMCL droplets (P = 0.002) before and after training, but higher individual IMCL area only before training (P = 0.013), compared with men. Women oxidized more fat (P = 0.027) and less carbohydrate (P = 0.032) throughout the study. Training increased Vo(2 peak) (P < 0.001), %fat oxidation (P = 0.018), SCHAD activity (P = 0.003), and CS activity (P = 0.042). In summary, endurance exercise training increased IMCL area density due to an increase in the number of lipid droplets, whereas the increase in total mitochondrial area was due to an increase in the size of individual mitochondrial fragments. In addition, women have higher IMCL content compared with men due mainly to a greater number of individual droplets. Finally, endurance exercise training increased the proportion of IMCL in physical contact with mitochondria.
380 citations
TL;DR: The identification of invertebrate TRP channels, whose genetic ablation alters thermally driven behaviors, makes it clear that thermosensation represents an evolutionarily conserved role of this ion channel family.
Abstract: Living organisms must evaluate changes in environmental and internal temperatures to mount appropriate physiological and behavioral responses conducive to survival Classical physiology has provided a wealth of information regarding the specialization of thermosensory functions among subclasses of peripheral sensory neurons and intrinsically thermosensitive neurons within the hypothalamus However, until recently, the molecular mechanisms by which these cells carry out thermometry have remained poorly understood The demonstration that certain ion channels of the transient receptor potential (TRP) family can be activated by increases or decreases in ambient temperature, along with the recognition of their heterogeneous expression patterns and heterogeneous temperature sensitivities, has led investigators to evaluate these proteins as candidate endogenous thermosensors Much of this work has involved one specific channel, TRP vanilloid 1 (TRPV1), which is both a receptor for capsaicin and related pungent vanilloid compounds and a "heat receptor," capable of directly depolarizing neurons in response to temperatures >42 degrees C Evidence for a contribution of TRPV1 to peripheral thermosensation has come from pharmacological, physiological, and genetic approaches In contrast, although capsaicin-sensitive mechanisms clearly influence core body temperature regulation, the specific contribution of TRPV1 to this process remains a matter of debate Besides TRPV1, at least six additional thermally sensitive TRP channels have been identified in mammals, and many of these also appear to participate in thermosensation Moreover, the identification of invertebrate TRP channels, whose genetic ablation alters thermally driven behaviors, makes it clear that thermosensation represents an evolutionarily conserved role of this ion channel family
359 citations
TL;DR: It is suggested thatACE2 is localized to the cytoplasm of neuronal cells in the brain and that ACE2 levels appear highly regulated by other components of the renin-angiotensin system, confirming its involvement in this system.
Abstract: Angiotensin-converting enzyme 2 (ACE2) is a newly discovered carboxy-peptidase responsible for the formation of vasodilatory peptides such as angiotensin-(1–7). We hypothesized that ACE2 is part of...
355 citations
TL;DR: A combination of caffeine and ephedrine has shown to be effective in long-term weight management, likely due to different mechanisms that may operate synergistically, e.g., respectively inhibiting the phosphodiesterase-induced degradation of cAMP and enhancing the sympathetic release of catecholamines.
Abstract: The global prevalence of obesity has increased considerably in the last decade. Tools for obesity management, including caffeine, ephedrine, capsaicin, and green tea have been proposed as strategies for weight loss and weight maintenance, since they may increase energy expenditure and have been proposed to counteract the decrease in metabolic rate that is present during weight loss. A combination of caffeine and ephedrine has shown to be effective in long-term weight management, likely due to different mechanisms that may operate synergistically, e.g., respectively inhibiting the phosphodiesterase-induced degradation of cAMP and enhancing the sympathetic release of catecholamines. However, adverse effects of ephedrine prevent the feasibility of this approach. Capsaicin has been shown to be effective, yet when it is used clinically it requires a strong compliance to a certain dosage, that has not been shown to be feasible yet. Also positive effects on body-weight management have been shown using green tea mixtures. Green tea, by containing both tea catechins and caffeine, may act through inhibition of catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here, the mechanisms may also operate synergistically. In addition, tea catechins have antiangiogenic properties that may prevent development of overweight and obesity. Furthermore, the sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general.
306 citations
TL;DR: Enhanced generation of mitochondrial ROS may be a common factor in the mechanism underlying denervation-induced atrophy in aging, mice lacking CuZn-SOD, and in the neurodegenerative disease, amyotrophic lateral sclerosis.
Abstract: Reactive oxygen species (ROS), especially mitochondrial ROS, are postulated to play a significant role in muscle atrophy. We report a dramatic increase in mitochondrial ROS generation in three cond...
304 citations
TL;DR: Neurons concentrated in the dorsal region of the DMH project directly to the rRP, a location corresponding to that of neurons trans-synaptically labeled from IBAT, and these neurons control nonshivering thermogenesis in rats, and their activation signals its recruitment in diverse experimental paradigms.
Abstract: Neurons in the dorsomedial hypothalamus (DMH) play key roles in physiological responses to exteroceptive (“emotional”) stress in rats, including tachycardia. Tachycardia evoked from the DMH or seen...
293 citations
TL;DR: Changes in baroreflex function with age are associated with an impaired ability of the organism to buffer changes in BP, evidenced by the reduced potentiation of the pressor response to bolus infusion of a pressor drug after compared to before systemic ganglionic blockade in older compared with young adults.
Abstract: Arterial blood pressure (BP) is regulated via the interaction of various local, humoral, and neural factors. In humans, the major neural pathway for acute BP regulation involves the baroreflexes. In response to baroreceptor activation/deactivation, as occurs during transient changes in BP, key determinants of BP, such as cardiac period/heart rate (via the sympathetic and parasympathetic nervous system) and vascular resistance (via the sympathetic nervous system), are modified to maintain BP homeostasis. In this review, the effects of aging on both the parasympathetic and sympathetic arms of the baroreflex are discussed. Aging is associated with decreased cardiovagal baroreflex sensitivity (i.e., blunted reflex changes in R-R interval in response to a change in BP). Mechanisms underlying this decrease may involve factors such as increased levels of oxidative stress, vascular stiffening, and decreased cardiac cholinergic responsiveness with age. Consequences of cardiovagal baroreflex impairment may include increased levels of BP variability, an impaired ability to respond to acute challenges to the maintenance of BP, and increased risk of sudden cardiac death. In contrast, baroreflex control of sympathetic outflow is not impaired with age. Collectively, changes in baroreflex function with age are associated with an impaired ability of the organism to buffer changes in BP. This is evidenced by the reduced potentiation of the pressor response to bolus infusion of a pressor drug after compared to before systemic ganglionic blockade in older compared with young adults.
282 citations
TL;DR: It seems that M. galloprovincialis lives close to its acclimation limits and incipient lethal temperature and that a small degree of warming will elicit stress responses at whole organism and molecular levels.
Abstract: The present study aimed to determine the thermal response of the Mediterranean mussel Mytilus galloprovincialis by integrating information from various levels of biological organization including b...
270 citations
TL;DR: It is concluded that short-term SIT induces rapid increases in skeletal muscle oxidative capacity but has divergent effects on proteins associated with glucose, lactate, and fatty acid transport.
Abstract: Skeletal muscle primarily relies on carbohydrate (CHO) for energy provision during high-intensity exercise. We hypothesized that sprint interval training (SIT), or repeated sessions of high-intensi...
TL;DR: Important steps are provided in determining the transcriptional and physiological endpoints of acute Cu toxicity in a model tropical species and suggesting that Cu alters normal mitochondrial biogenic processes, possibly though metallochaperones like COX-17.
Abstract: In fish, environmental pollution is one factor that induces oxidative stress, and this can disturb the natural antioxidant defense system. Oxidative stress has been well characterized in vitro, yet...
TL;DR: These results implicate the POA, DMH, and rRPa in the central efferent pathways for thermogenic, metabolic, and cardiac responses to skin cooling, and suggest that these pathways can be modulated by serotonergic inputs to the medullary raphe.
Abstract: Control of thermoregulatory effectors by the autonomic nervous system is a critical component of rapid cold-defense responses, which are triggered by thermal information from the skin. However, the central autonomic mechanism driving thermoregulatory effector responses to skin thermal signals remains to be determined. Here, we examined the involvement of several autonomic brain regions in sympathetic thermogenic responses in brown adipose tissue (BAT) to skin cooling in urethane-chloralose-anesthetized rats by monitoring thermogenic [BAT sympathetic nerve activity (SNA) and BAT temperature], metabolic (expired CO(2)), and cardiovascular (arterial pressure and heart rate) parameters. Acute skin cooling, which did not reduce either rectal (core) or brain temperature, evoked increases in BAT SNA, BAT temperature, expired CO(2), and heart rate. Skin cooling-evoked thermogenic, metabolic, and heart rate responses were inhibited by bilateral microinjections of bicuculline (GABA(A) receptor antagonist) into the preoptic area (POA), by bilateral microinjections of muscimol (GABA(A) receptor agonist) into the dorsomedial hypothalamic nucleus (DMH), or by microinjection of muscimol, glycine, 8-OH-DPAT (5-HT(1A) receptor agonist), or kynurenate (nonselective antagonist for ionotropic excitatory amino acid receptors) into the rostral raphe pallidus nucleus (rRPa) but not by bilateral muscimol injections into the lateral/dorsolateral part or ventrolateral part of the caudal periaqueductal gray. These results implicate the POA, DMH, and rRPa in the central efferent pathways for thermogenic, metabolic, and cardiac responses to skin cooling, and suggest that these pathways can be modulated by serotonergic inputs to the medullary raphe.
TL;DR: A critical role for a TLR4-HMGB1 pathway is demonstrated in the initiation of systemic inflammation and end-organ injury following isolated peripheral tissue injury.
Abstract: High-mobility group box 1 (HMGB1) is a 30-kDa DNA-binding protein that displays proinflammatory cytokine-like properties. HMGB1-dependent inflammatory processes have been demonstrated in models of ...
TL;DR: The aim of this review is to critically summarize the evidence available to support an independent association between OSAS and cardiovascular disease.
Abstract: Several studies have shown the occurrence of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease, including arterial hypertension, ischemic heart disease, and stroke. The pathogenesis of the cardiovascular complications of OSAS is still poorly understood, however. Several mechanisms are likely to be involved, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormality in the process of coagulation, and metabolic dysregulation. The latter may involve insulin resistance and disorders of lipid metabolism. The aim of this review, which reports the data presented at a workshop jointly endorsed by the European Society of Hypertension and by the European Union COST action on OSAS (COST B26), is to critically summarize the evidence available to support an independent association between OSAS and cardiovascular disease.
TL;DR: In this paper, the effect of two different intense exercise training regimens on skeletal muscle ion transport systems, performance, and metabolic response to exercise was examined, and 13 subjects perfo...
Abstract: This study examined the effect of two different intense exercise training regimens on skeletal muscle ion transport systems, performance, and metabolic response to exercise. Thirteen subjects perfo...
TL;DR: The hypothesis that curcumin can reduce inflammation and offset some of the performance deficits associated with eccentric exercise-induced muscle damage is supported.
Abstract: Downhill running is associated with fiber damage, inflammation, delayed-onset muscle soreness, and various functional deficits. Curcumin, a constituent of the Indian spice turmeric has been investi...
TL;DR: It is concluded that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood.
Abstract: Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adu...
TL;DR: Investigating how paradoxical sleep deprivation for 24 and 96 h and sleep restriction for 21 days by the modified multiple-platform method, and their respective 24-h recovery periods, affect immune activation in rats revealed alterations during sleep deprivation suggest only minor alterations of nonspecific immune parameters during acute PSD, and a significant impairment in cellular response during chronic SR.
Abstract: Sleep deprivation is now recognized as an increasingly common condition inherent to modern society, and one that in many ways, is detrimental to certain physiological systems, namely, immune function. Although sleep is now viewed by a significant body of researchers as being essential for the proper working of a host of defense systems, the consequences of a lack of sleep on immune function remains to be fully comprehended. The aim of the current study was to investigate how paradoxical sleep deprivation (PSD) for 24 and 96 h and sleep restriction (SR) for 21 days by the modified multiple-platform method, and their respective 24-h recovery periods, affect immune activation in rats. To this end, we assessed circulating white blood cell counts, lymphocyte count within immune organs, as well as Ig and complement production. The data revealed that PSD for 96 h increased complement C3 and corticosterone concentration in relation to the control group. In contrast, the spleen weight, total leukocytes, and lymphocytes decreased during SR for 21 days when compared with the control group, although production of a certain class of immunoglobulin, the IgM, did increase. After recovery sleep, lymphocyte count in axillary lymph nodes grew when rats had rebound sleep after PSD for 24 h, neutrophils increased after PSD 96 h and lymphocytes numbers were higher after SR 21 days. Such alterations during sleep deprivation suggest only minor alterations of nonspecific immune parameters during acute PSD, and a significant impairment in cellular response during chronic SR.
TL;DR: CD36 deletion decreased fat consumption and enhanced the ability of the mice to compensate for the calories provided by their optional fat intake, which support CD36 mediation of a gustatory component to fat preference but demonstrate that it is not essential for fat-conditioned flavor preferences.
Abstract: Several findings suggest the existence of a “fatty” taste, and the CD36 fatty acid translocase is a candidate taste receptor. The present study compared fat preference and acceptance in CD36 knocko...
TL;DR: Diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats, and shows that insulinensitivity of glucose and fat metabolism can be differentially regulated in cats.
Abstract: Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.
TL;DR: The relative contribution of the autoregulatory mechanisms determines the amount and spectrum of pressure fluctuations reaching glomerular and postglomerular capillaries and thereby potentially impinge on filtration, reabsorption, medullary perfusion, and hypertensive renal damage.
Abstract: Autoregulation of renal blood flow (RBF) is caused by the myogenic response (MR), tubuloglomerular feedback (TGF), and a third regulatory mechanism that is independent of TGF but slower than MR. Th...
TL;DR: Although there was no difference in relative heart weights between control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes inPR fetuses and the relative sparing of the growth of individual cardiomeocytes in the growth-restricted fetus are adaptations that may have long-term consequences for heart development in postnatal life.
Abstract: Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placen...
TL;DR: HSP27 and alpha B-crystallin seemed to respond immediately to maximal eccentric exercise by binding to cytoskeletal/myofibrillar proteins, probably to function as stabilizers of disrupted myofibrillsar structures.
Abstract: In this study the stress protein response to unaccustomed maximal eccentric exercise in humans was investigated. Eleven healthy males performed 300 maximal eccentric actions with the quadriceps mus...
TL;DR: Healthy aged humans failed to maintain T(es) during mild cold stress; however, the mechanisms underlying this response are not clear.
Abstract: Aged humans often exhibit an impaired defense of core temperature during cold stress. However, research documenting this response has typically used small subject samples and strong cold stimuli. T...
TL;DR: The present review addresses possible sex-related differences in urine volume and osmolality (U(osm) that could participate in this male risk predominance to urolithiasis and hypertension and to the faster progression towards end-stage renal failure.
Abstract: Men are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women. Previous studies suggest that greater urine concentration is associated with acceleration of pr...
TL;DR: In this study, morpholino-modified antisense oligonucleotides are used to knockdown the gene product of H(+)-ATPase subunit A and the phenotype of the mutants revealed several abnormalities, including suppression of acid-secretion from skin, growth retardation, trunk deformation, and loss of internal Ca(2+) and Na(+).
Abstract: In the skin of zebrafish embryo, the vacuolar H+-ATPase (V-ATPase, H+ pump) distributed mainly in the apical membrane of H+-pump-rich cells, which pump internal acid out of the embryo and function ...
TL;DR: In this article, the development of hypertension is associated with vascular dysfunction characterized by impaired vasodilatation to nitric oxide, exaggerated vasoconstriction to ANG II, and microvascular dysfunction.
Abstract: Developmental programming of hypertension is associated with vascular dysfunction characterized by impaired vasodilatation to nitric oxide, exaggerated vasoconstriction to ANG II, and microvascular...
TL;DR: It is concluded that obestatin does not act in pituitary gland to regulate GH secretion but may act in brain to alter thirst mechanisms, and in rats the effects of obstatin on food intake may be secondary to an action of the peptide to inhibit water drinking.
Abstract: Derived from the same prohormone, obestatin has been reported to exert effects on food intake that oppose those of ghrelin. The obestatin receptor GPR39 is present in brain and pituitary gland. Since the gene encoding those two peptides is expressed also in those tissues, we examined further the possible actions of obestatin in vivo and in vitro. Intracerebroventricular administration of obestatin inhibited water drinking in ad libitum-fed and -watered rats, and in food-and water-deprived animals. The effects on water drinking preceded and were more pronounced than any effect on food intake, and did not appear to be the result of altered locomotor/behavioral activity. In addition, obestatin inhibited ANG II-induced water drinking in animals provided free access to water and food. Current-clamp recordings from cultured, subfornical organ neurons revealed significant effects of the peptide on membrane potential, suggesting this as a potential site of action. In pituitary cell cultures, log molar concentrations of obestatin ranging from 1.0 pM to 100 nM failed to alter basal growth hormone (GH) secretion. In addition, 100 nM obestatin failed to interfere with the stimulation of GH secretion by GH-releasing hormone or ghrelin and did not alter the inhibition by somatostatin in vitro. We conclude that obestatin does not act in pituitary gland to regulate GH secretion but may act in brain to alter thirst mechanisms. Importantly, in rats the effects of obestatin on food intake may be secondary to an action of the peptide to inhibit water drinking.
TL;DR: It is concluded that severe hypoxia exacerbates peripheral fatigue of limb locomotor muscles and that this effect may contribute, in part, to the early termination of exercise.
Abstract: We hypothesized that severe hypoxia limits exercise performance via decreased contractility of limb locomotor muscles. Nine male subjects [mean ± SE maximum O2 uptake (Vo2 max) = 56.5 ± 2.7 ml·kg−...