4,520 research outputs found
Epigenetic Regulation of Biological Rhythms : An Evolutionary Ancient Molecular Timer
The author thanks Barbara Helm, John OâNeill and Brian Prendergast for constructive comments on a previous version of the manuscript.Peer reviewedPostprin
An Integrated Analysis of the Physiological Effects of Space Flight: Executive Summary
A large array of models were applied in a unified manner to solve problems in space flight physiology. Mathematical simulation was used as an alternative way of looking at physiological systems and maximizing the yield from previous space flight experiments. A medical data analysis system was created which consist of an automated data base, a computerized biostatistical and data analysis system, and a set of simulation models of physiological systems. Five basic models were employed: (1) a pulsatile cardiovascular model; (2) a respiratory model; (3) a thermoregulatory model; (4) a circulatory, fluid, and electrolyte balance model; and (5) an erythropoiesis regulatory model. Algorithms were provided to perform routine statistical tests, multivariate analysis, nonlinear regression analysis, and autocorrelation analysis. Special purpose programs were prepared for rank correlation, factor analysis, and the integration of the metabolic balance data
TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria
The 18-kDa translocator protein (TSPO) localizes in the outer mitochondrial membrane (OMM) of cells and is readily up-regulated under various pathological conditions such as cancer, inflammation, mechanical lesions and neurological diseases. Able to bind with high affinity synthetic and endogenous ligands, its core biochemical function resides in the translocation of cholesterol into the mitochondria influencing the subsequent steps of (neuro-)steroid synthesis and systemic endocrine regulation. Over the years, however, TSPO has also been linked to core cellular processes such as apoptosis and autophagy. It interacts and forms complexes with other mitochondrial proteins such as the voltage-dependent anion channel (VDAC) via which signalling and regulatory transduction of these core cellular events may be influenced. Despite nearly 40 years of study, the precise functional role of TSPO beyond cholesterol trafficking remains elusive even though the recent breakthroughs on its high-resolution crystal structure and contribution to quality-control signalling of mitochondria. All this along with a captivating pharmacological profile provides novel opportunities to investigate and understand the significance of this highly conserved protein as well as contribute the development of specific therapeutics as presented and discussed in the present review
Circadian and Metabolic Effects of Light: Implications in Weight Homeostasis and Health
Daily interactions between the hypothalamic circadian clock at the suprachiasmatic nucleus (SCN) and peripheral circadian oscillators regulate physiology and metabolism to set temporal variations in homeostatic regulation. Phase coherence of these circadian oscillators is achieved by the entrainment of the SCN to the environmental 24-h light:dark (LD) cycle, coupled through downstream neural, neuroendocrine, and autonomic outputs. The SCN coordinate activity and feeding rhythms, thus setting the timing of food intake, energy expenditure, thermogenesis, and active and basal metabolism. In this work, we will discuss evidences exploring the impact of different photic entrainment conditions on energy metabolism. The steady-state interaction between the LD cycle and the SCN is essential for health and wellbeing, as its chronic misalignment disrupts the circadian organization at different levels. For instance, in nocturnal rodents, non-24 h protocols (i.e., LD cycles of different durations, or chronic jet-lag simulations) might generate forced desynchronization of oscillators from the behavioral to the metabolic level. Even seemingly subtle photic manipulations, as the exposure to a "dim light" scotophase, might lead to similar alterations. The daily amount of light integrated by the clock (i.e., the photophase duration) strongly regulates energy metabolism in photoperiodic species. Removing LD cycles under either constant light or darkness, which are routine protocols in chronobiology, can also affect metabolism, and the same happens with disrupted LD cycles (like shiftwork of jetlag) and artificial light at night in humans. A profound knowledge of the photic and metabolic inputs to the clock, as well as its endocrine and autonomic outputs to peripheral oscillators driving energy metabolism, will help us to understand and alleviate circadian health alterations including cardiometabolic diseases, diabetes, and obesity.Fil: Plano, Santiago AndrĂ©s. Pontificia Universidad CatĂłlica Argentina "Santa MarĂa de los Buenos Aires". Instituto de Investigaciones BiomĂ©dicas. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Garcia Moro, Paula. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Golombek, Diego AndrĂ©s. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Chiesa, Juan JosĂ©. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa. Laboratorio de CronobiologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentin
Clock genes, pancreatic function and diabetes
Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic ÎČ cells, glucose homeostasis, and diabetes.This work was supported by grants from the Ministerio de EconomĂa (BFU2013-42789)This work was supported by grants from Generalitat Valenciana (PROMETEO/2011/080
Endocrinology and the brain: Corticotropin-Releasing Hormone signaling
Corticotropin-releasing hormone (CRH) is a key player of basal and stress activated responses in the hypothalamic-pituitary-adrenal axis (HPA) and in extrahypothalamic circuits, where it functions as a neuromodulator to orchestrate humoral and behavioral adaptive responses to stress. This review describes molecular components and cellular mechanisms involved in CRH signaling downstream of its G protein-coupled receptors (GPCRs) CRHR1 and CRHR2, and summarizes recent findings that challenge the classical view of GPCR signaling, and impact on our understanding of CRHRs function. Special emphasis is placed on recent studies of CRH signaling that revealed new mechanistic aspects of cAMP generation and ERK1/2 activation in physiologically relevant contexts of the neurohormone action. In addition, we present an overview of the pathophysiological role of the CRH system, which highlights the need for a precise definition of CRHRs signaling at molecular level to identify novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders.Fil: Inda, MarĂa Carolina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de InvestigaciĂłn en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de FisiologĂa, BiologĂa Molecular y Celular; ArgentinaFil: Armando, Natalia Giannina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de InvestigaciĂłn en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Dos Santos Claro, Paula Ayelen. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de InvestigaciĂłn en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Silberstein Cuña, Susana Iris. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de InvestigaciĂłn en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de FisiologĂa, BiologĂa Molecular y Celular; Argentin
Obesity and the Effects of Excess Adiposity on Bone Properties, Health, and Function
This article aims to inform on the relationships that exist between obesity, a fairly modern ailment to the human species, and bone mechanical properties and function. Because the phenomenon that is obesity is so contemporary, itâs progressive effects on the skeletal system are poorly understood. Many previous studies aimed to prove that obesity had a positive effect on bone mass. It was believed that obesity and the excess body mass attributed to it essentially increased BMD by presenting load bearing bones with higher levels of stress than their non-obese counterparts, but this assumption of a positive correlation seems to be confounded by a variety of biological and endocrinological factors. The following sections will explore the effects that diets high in saturated fats and its consequence, obesity, have on the absorption of dietary calcium. This flaw in the absorption of dietary calcium may mean the decreasing ability of bone, particularly trabecular bone, to maintain proper density and in turn, become increasingly brittle. Combined with the increase in mechanical loading regimes that excess adiposity may present weight-bearing bones with, an understanding of these combined effects on bone biology is pivotal. This paper will also explore the relationships that exist between obesity, serum leptin levels and inflammatory responses, and bone properties. All of these factors (calcium absorption, leptin, and inflammatory responses) are important for bone growth, function, and mechanics, especially in respect to senescence. The previously mentioned âside effectsâ of obesity are also recognized as factors in the initiation of osteoporosis. Consequently, there must exist a relationship between obesity and osteoporosis. The bulk of this article will further explore this refined relationship in order to prove that the effects of obesity are indeed deleterious to health, and ultimately, to the function of bone as well
L-Arginine promotes gut hormone release and reduces food intake in rodents
Aims: To investigate the anorectic effect of Lâarginine (LâArg) in rodents.
Methods: We investigated the effects of LâArg on food intake, and the role of the anorectic gut hormones glucagonâlike peptideâ1 (GLPâ1) and peptide YY (PYY), the Gâproteinâcoupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents.
Results: Oral gavage of LâArg reduced food intake in rodents, and chronically reduced cumulative food intake in dietâinduced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. LâArg stimulated GLPâ1 and PYY release in vitro and in vivo. Pharmacological blockade of GLPâ1 and PYY receptors did not influence the anorectic effect of LâArg. LâArgâmediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of LâArg suppressed food intake in rats.
Conclusions: LâArg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of LâArg is unlikely to be mediated by GLPâ1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of LâArg suppressed food intake in rats, suggesting that LâArg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which LâArg suppresses food intake and its utility in the treatment of obesity
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