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Metabolic Perturbations (metabolic + perturbation)
Selected AbstractsDifferential Role of Corticotrophin-Releasing Factor Receptor Types 1 and 2 in Stress-Induced Suppression of Pulsatile Luteinising Hormone Secretion in the Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006X. F. Li Corticotrophin-releasing factor (CRF) plays a pivotal role in stress-induced suppression of the gonadotrophin-releasing hormone pulse generator. We have previously shown that type 2 CRF receptors (CRF2) mediate restraint stress-induced suppression of luteinising hormone (LH) pulses in the rat. The present study aimed: (i) to determine whether type 1 CRF receptors (CRF1) are also involved in this response to restraint and (ii) to investigate the differential involvement of CRF1 and CRF2 in the suppression of LH pulses in response to the metabolic perturbation of insulin-induced hypoglycemia and the innate immunological challenge of lipopolysaccharide (LPS). Ovariectomised rats with oestrogen replacement were implanted with intracerebroventricular (i.c.v.) and intravenous (i.v.) cannulae. Blood samples (25 µl) were collected every 5 min for 5 h for LH measurement. After 2 h of controlled blood sampling, rats were either exposed to restraint (1 h) or injected intravenously with insulin (0.25 IU/kg) or LPS (5 µg/kg). All three stressors suppressed LH pulses. The CRF1 antagonist SSR125543Q (11.5 µmol/rat i.v., 30 min before stressor) blocked the inhibitory response to restraint, but not hypoglycaemia or LPS stress. In addition to its effect on restraint, the CRF2 antagonist astressin2 -B (28 nmol/rat i.c.v., 10 min before insulin or LPS) blocked hypoglycaemia or LPS stress-induced suppression of LH pulses. These results suggest that hypoglycaemia and LPS stress-induced LH suppression involves activation of CRF2 while restraint stress-induced inhibition of LH pulses involves both CRF1 and CRF2. [source] Arabidopsis transcript and metabolite profiles: ecotype-specific responses to open-air elevated [CO2]PLANT CELL & ENVIRONMENT, Issue 11 2008PINGHUA LI ABSTRACT A Free-Air CO2 Enrichment (FACE) experiment compared the physiological parameters, transcript and metabolite profiles of Arabidopsis thaliana Columbia-0 (Col-0) and Cape Verde Island (Cvi-0) at ambient (,0.375 mg g,1) and elevated (,0.550 mg g,1) CO2 ([CO2]). Photoassimilate pool sizes were enhanced in high [CO2] in an ecotype-specific manner. Short-term growth at elevated [CO2] stimulated carbon gain irrespective of down-regulation of plastid functions and altered expression of genes involved in nitrogen metabolism resembling patterns observed under N-deficiency. The study confirmed well-known characteristics, but the use of a time course, ecotypic genetic differences, metabolite analysis and the focus on clusters of functional categories provided new aspects about responses to elevated [CO2]. Longer-term Cvi-0 responded by down-regulating functions favouring carbon accumulation, and both ecotypes showed altered expression of genes for defence, redox control, transport, signalling, transcription and chromatin remodelling. Overall, carbon fixation with a smaller commitment of resources in elevated [CO2] appeared beneficial, with the extra C only partially utilized possibly due to disturbance of the C : N ratio. To different degrees, both ecotypes perceived elevated [CO2] as a metabolic perturbation that necessitated increased functions consuming or storing photoassimilate, with Cvi-0 emerging as more capable of acclimating. Elevated [CO2] in Arabidopsis favoured adjustments in reactive oxygen species (ROS) homeostasis and signalling that defined genotypic markers. [source] Alterations in electrolyte equilibrium in patients with acute leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005Theodosios D. Filippatos Abstract:,Background and aim:,A wide array of disturbances in electrolyte equilibrium is commonly seen in patients with acute leukemia (AL). These abnormalities present a potential hazard in these patients, as that of enhancing the cardiotoxic effects of certain chemotherapeutic regimens. The literature dealing with AL-related electrolyte abnormalities and their interactions in leukemic patients was reviewed. Data synthesis:,Sources included MEDLINE and EMBASE. The search strategy was based on the combination of ,acute leukemia', ,electrolyte abnormalities', ,acid-base disorders', ,potassium', ,sodium', ,magnesium', ,calcium', and ,phosphorus'. References of retrieved articles were also screened. A decrease in serum potassium, mainly owing to lysozyme-induced tubular damage, appears to be one of the most frequent and potentially hazardous abnormalities. Other clinically significant metabolic perturbations include hyponatremia and hypercalcemia. Conclusion:,A broad spectrum of electrolyte abnormalities is encountered in the clinical setting of AL, which are related to the disease process per se and/or to the therapeutic interventions. Clinicians should be vigilant for early detection and appropriate management of these disorders before the initiation of chemotherapy regimens as well as during treatment. [source] Axonal integrity in the absence of functional peroxisomes from projection neurons and astrocytesGLIA, Issue 13 2010Astrid Bottelbergs Abstract Ablation of functional peroxisomes from all neural cells in Nestin-Pex5 knockout mice caused remarkable neurological abnormalities including motoric and cognitive malfunctioning accompanied by demyelination, axonal degeneration, and gliosis. An oligodendrocyte selective Cnp-Pex5 knockout mouse model shows a similar pathology, but with later onset and slower progression. Until now, the link between these neurological anomalies and the known metabolic alterations, namely the accumulation of very long-chain fatty acids (VLCFA) and reduction of plasmalogens, has not been established. We now focused on the role of peroxisomes in neurons and astrocytes. A neuron-specific peroxisome knockout model, NEX-Pex5, showed neither microscopic nor metabolic abnormalities indicating that the lack of functional peroxisomes within neurons does not cause axonal damage. Axonal integrity and normal behavior was also preserved when peroxisomes were deleted from astrocytes in GFAP-Pex5,/, mice. Nevertheless, peroxisomal metabolites were dysregulated in brain including a marked accumulation of VLCFA and a slight reduction in plasmalogens. Interestingly, despite minor targeting of oligodendrocytes in GFAP-Pex5,/, mice, these metabolic perturbations were also present in isolated myelin indicating that peroxisomal metabolites are shuttled between different brain cell types. We conclude that absence of peroxisomal metabolism in neurons and astrocytes does not provoke the neurodegenerative phenotype observed after deleting peroxisomes from oligodendrocytes. Lack of peroxisomal metabolism in astrocytes causes increased VLCFA levels in myelin, but this has no major impact on neurological functioning. © 2010 Wiley-Liss, Inc. [source] Influence of Serotonin on the Development and Migration of Gonadotropin-Releasing Hormone Neurones in Rat FoetusesJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2003T. Pronina Abstract This study used a pharmacological approach to evaluate the consequences of the metabolic perturbations of neurotransmitters on brain development. Pregnant rats received p-chlorophenylalanine (pCPA), an inhibitor of serotonin (5-hydroxytryptamine, 5-HT) synthesis, or saline (control) from the 11th day of gestation once or daily up to the 15th, 17th and 20th day, followed by processing of the forebrain and/or nasal cranium of foetal males and females for high-performance liquid chromatography of monoamines, radioimmunoassay of gonadotropin-releasing hormone (GnRH) and quantitative and semiquantitative immunocytochemistry for GnRH. The pCPA treatment resulted in a 50,70% depletion of 5-HT in the nasal crania and forebrains at any studied age. Radioimmunoassay showed no change in GnRH content in 5-HT deficient foetuses at E16 compared to controls, being higher in both cases in the rostral forebrain than in the hypothalamus. In controls at E21, the GnRH content in the hypothalamus exceeded that in the rostral forebrain, whereas in the 5-HT deficient group the opposite was found. These data suggest that 5-HT provided a stimulating effect on GnRH neurone migration, and this was confirmed by quantification of GnRH-immunoreactive neurones in the forebrain along the trajectory of their migration. At E18 and E21, the fractions of GnRH neurones in the rostral part of the trajectory in pCPA-treated foetuses were greater than those in control foetuses but the opposite was true for the caudal part of the trajectory. Moreover, 5-HT appeared to control the proliferation of the precursor cells of GnRH neurones and their differentiation, as derived from the observations of the increased number of GnRH neurones in the forebrain of foetuses of both sexes, as well as the region-specific decreased neuronal size and content of GnRH in 5-HT-deficient females. Thus, 5-HT appears to contribute to the regulation of the origin, differentiation and migration of GnRH neurones. [source] Fuel sensing and the central nervous system (CNS): implications for the regulation of energy balance and the treatment for obesityOBESITY REVIEWS, Issue 3 2005R. J. Seeley Summary This review describes the product of the 3-day International Association for the Study of Obesity (IASO) Stock Conference held in March 2004 and sponsored by Abbott Laboratories. The conference was focused on how the mechanisms by which individual cells sense their own fuel status might influence the energy balance of the entire organism. Whether you are a single-celled organism or a sophisticated mammal with a large cerebral cortex, it is critical that cellular activity be matched to the available fuel necessary for that activity. Rapid progress has been made in the last decade in our understanding of the critical metabolic events that cells monitor to accomplish this critical task. More recent developments have begun to apply this understanding to how critical populations of neurones may monitor similar events to control both food intake and energy expenditure. The picture that emerges is that numerous peripheral fuel sensors communicate to the central nervous system (CNS) via neural and humoral routes. Moreover, it has been known for decades that specific populations of neurones sense changes in ambient glucose levels and adjust their firing rate in response and changes in neuronal glucose metabolism can influence energy balance. The CNS, however, does not just sense glucose but rather appears to be sensitive to a wide range of metabolic perturbations associated with fuel availability. This information is used to adjust both caloric intake and the disposition of fuels in the periphery. Increased understanding of these CNS fuel-sensing mechanisms may lead to novel therapeutic targets for obesity. [source] Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptationAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Carol A. Shively Abstract Abdominal obesity is prevalent and often accompanied by an array of metabolic perturbations including elevated blood pressure, dyslipidemia, impaired glucose tolerance or insulin resistance, a prothrombotic state, and a proinflammatory state, together referred to as the metabolic syndrome. The metabolic syndrome greatly increases coronary heart disease (CHD) risk. Social stress also increases CHD although the mechanisms through which this occurs are not completely understood. Chronic stress may result in sustained glucocorticoid production, which is thought to promote visceral obesity. Thus, one hypothesis is that social stress may cause visceral fat deposition and the metabolic syndrome, which, in turn increases CHD. CHD is caused by coronary artery atherosclerosis (CAA) and its sequelae. Cynomolgus monkeys (Macaca fascicularis) are a well-established models of CAA. Social subordination may be stressful to cynomolgus monkeys and result in hypercortisolemia and exacerbated CAA in females. Herein is reviewed a body of literature which suggests that social stress increases visceral fat deposition in cynomolgus monkeys, that subordinate females are more likely than dominants to have visceral obesity, that females with visceral obesity have behavioral and physiological characteristics consistent with a stressed state, and that females with high ratios of visceral to subcutaneous abdominal fat develop more CAA. While these relationships have been most extensively studied in cynomolgus macaques, obesity-related metabolic disturbances are also observed in other primate species. Taken together, these observations support the view that the current obesity epidemic is the result of a primate adaptation involving the coevolution with encephalization of elaborate physiological systems to protect against starvation and defend stored body fat in order to feed a large and metabolically demanding brain. Social stress may be engaging these same physiological systems, increasing the visceral deposition of fat and its sequelae, which increase CHD risk. Am. J. Primatol. 71:742,751, 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||