1,721,060 research outputs found
Vagal nerve stimulation can elicit both activation and inhibition of brown adipose tissue sympathetic nerve activity (1131.6)
No full textThe dependence of BAT thermogenesis on the availability of metabolic substrates suggests that metabolic signals from the viscera could influence the sympathetic outflow driving BAT thermogenesis. Viscerosensory afferents in the proximal end of the sectioned left cervical vagus nerve were activated with electrical stimulation in anesthetized, ventilated rats while recording the SNA to the contralateral interscapular BAT pad. Paired-pulse VNS delivered once every 5 sec evoked excitatory evoked potentials in BAT SNA with a peak latency of ~ 180 ms, followed by a ~2 s period of quiescent BAT SNA. Within a few seconds of stimulus onset, continuous, single-pulse VNS at 2 Hz produced a complete inhibition of cold-evoked BAT SNA that was sustained for at least 2 hrs of maintained VNS. Similarly, activation of neurons in the intermediate nucleus of the solitary tract (iNTS), at the level of the area postrema, with nanoinjections (60 pmol) of bicuculline also inhibits the VNS-evoked excitation of BAT SNA. Inhibition of neurons in the rostral ventromedial medullary raphe pallidus region also eliminates the VNS-evoked excitation of BAT SNA. These data support the existence of populations of vagal afferents whose stimulation can (1) increase BAT SNA via activation of BAT sympathetic premotor neurons or (2) inhibit BAT SNA via activation of BAT sympathoinhibitory neurons in the iNTS (see Am. J. Physiol. Regul. Integr. Comp. Physiol., 299:R277-R290, 2010. PMC2904145)
α2 adrenergic receptor-mediated inhibition of thermogenesis
No full text�2 adrenergic receptor (�2-AR) agonists have been used as antihypertensive agents, in the management of drug withdrawal, and as sedative analgesics. Since �2-AR agonists also influence the regulation of body temperature, we explored their potential as antipyretic agents. This study delineates the central neural substrate for the inhibition of rat brown adipose tissue (BAT) and shivering thermogenesis by �2-AR agonists. Nanoinjection of the �2-AR agonist clonidine (1.2 nmol) into the rostral raphe pallidus area (rRPa) inhibited BAT sympathetic nerve activity (SNA) and BAT thermogenesis. Subsequent nanoinjection of the �2-AR antagonist idazoxan (6 nmol) into the rRPa reversed the clonidine-evoked inhibition of BAT SNA and BAT thermogenesis. Systemic administration of the �2-AR agonists dexmedetomidine (25 �g/kg, i.v.) and clonidine (100 �g/kg, i.v.) inhibited shivering EMGs, BAT SNA, and BAT thermogenesis, effects that were reversed by nanoinjection of idazoxan (6 nmol) into the rRPa. Dexmedetomidine (100 �g/kg, i.p.) prevented and reversed lipopolysaccharide-evoked (10 �g/kg, i.p.) thermogenesis in free-behaving rats. Cholera toxin subunit b retrograde tracing from rRPa and pseudorabies virus transynaptic retrograde tracing from BAT combined with immunohistochemistry for catecholaminergic biosynthetic enzymes revealed the ventrolateral medulla as the source of catecholaminergic input to the rRPa and demonstrated that these catecholaminergic neurons are synaptically connected to BAT. Photostimulation of ventrolateral medulla neurons expressing the PRSx8- ChR2-mCherry lentiviral vector inhibited BAT SNA via activation of 2-ARs in the rRPa. These results indicate a potent inhibition of BAT and shivering thermogenesis by �2-AR activation in the rRPa, and suggest a therapeutic potential of �2-AR agonists for reducing potentially lethal elevations in body temperature during excessive fever. � 2013 the authors
Triple-helix formation at different positions on nucleosomal DNA
No full textWe have prepared a series of seven DNA fragments, based on the 160 base- pair tyrT sequence, which contain 12-14 base-pair oligopurine tracts at different positions, and have examined their availability for triple-helix formation after reconstituting onto nucleosome core particles. By using DNase I footprinting we find that in general, triplexes can only be formed at sites located toward the ends of nucleosomal DNA fragments. For the native fragment, bases 1-145 are in contact with the protein surface. Stable triplexes can be formed on these nucleosome-bound fragments for sites located before position 33 and beyond position 94. These are formed with both CT- containing oligonucleotides, generating parallel triplexes at pH 5.5, and GT- containing oligonucleotides forming antiparallel triplexes at pH 7.5. No antiparallel triplexes were formed at sites located between these positions. Parallel triplexes were also not formed at sites between positions 39-50 and 43-54 with oligonucleotide concentrations as high as 30 μM. However parallel triplex formation was evident at a site between positions 48 and 59, albeit with a reduced affinity compared to free DNA, suggesting that this oligopurine tract is less tightly associated with the nucleosome surface or that it has an altered translational position. The introduction of an oligopurine tract in the vicinity of the nucleosome dyad caused the fragment to adopt a different nucleosomal position, which could be targeted with parallel, but not antiparallel triplexes.</p
Orexin modulates brown adipose tissue thermogenesis
Full text linkNon-shivering thermogenesis in brown adipose tissue (BAT) plays an important role in thermoregulation. In addition, activations of BAT have important implications for energy homeostasis due to the metabolic consumption of energy reserves entailed in the production of heat in this tissue. In this conceptual overview we describe the role of orexins/hypocretins within the central nervous system in the modulation of thermogenesis in BAT under several physiological conditions. Within this framework, we consider potential neural mechanisms underlying the pathological conditions associated with the absence of the central orexinergic modulation of BAT thermogenesis and energy expenditure. Overall, the experimental basis for our understanding of the role of central orexin in regulating body temperature and energy homeostasis provides an illustrative example that highlights several general principles and caveats that should help to guide future investigations of the neurochemical regulation of thermogenesis and metabolism
Central activation of the A1 adenosine receptor (A1AR) induces a hypothermic, torpor-like state in the rat
No full textSince central activation of A1 adenosine receptors (A1ARs) plays an important role in the induction of the hypothermic and hypometabolic torpid state in hibernating mammals, we investigated the potential for the A1AR agonist N6-cyclohexyladenosine to induce a hypothermic, torpor-like state in the (nonhibernating) rat. Core and brown adipose tissue temperatures, EEG, heart rate, and arterial pressure were recorded in free-behaving rats, and c-fos expression in the brain was analyzed, following central administration of N6-cyclohexyladenosine. Additionally, we recorded the sympathetic nerve activity to brown adipose tissue; expiratory CO2 and skin, core, and brown adipose tissue temperatures; and shivering EMGs in anesthetized rats following central and localized, nucleus of the solitary tract, administration of N6-cyclohexyladenosine. In rats exposed to a cool (15�C) ambient temperature, central A1AR stimulation produced a torpor-like state similar to that in hibernating species and characterized by a marked fall in body temperature due to an inhibition of brown adipose tissue and shivering thermogenesis that is mediated by neurons in the nucleus of the solitary tract. During the induced hypothermia, EEG amplitude and heart rate were markedly reduced. Skipped heartbeats and transient bradycardias occurring during the hypothermia were vagally mediated since they were eliminated by systemic muscarinic receptor blockade. These findings demonstrate that a deeply hypothermic, torpor-like state can be pharmacologically induced in a nonhibernating mammal and that recovery of normothermic homeostasis ensues upon rewarming. These results support the potential for central activation of A1ARs to be used in the induction of a hypothermic, therapeutically beneficial state in humans. � 2013 the authors
An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis
No full textNon-shivering thermogenesis in brown adipose tissue (BAT) plays an important role in thermoregulatory cold-defense and, through its metabolic consumption of energy reserves to produce heat, can affect the long-term regulation of adiposity. An orexinergic pathway from the perifornical lateral hypothalamus (PeF/LH) to the rostral raphe pallidus (rRPa) has been demonstrated to increase the gain of the excitatory drives to medullary sympathetic premotor neurons controlling BAT sympathetic outflow and BAT thermogenesis. With this background, we consider neural mechanisms that could underlie orexin's modulation of the excitability of BAT sympathetic premotor neurons in rRPa and the potential role of altered BAT thermogenesis in pathological conditions associated with the absence of the central orexin system. Overall, these new data enhance our understanding of the role of central orexin in regulating body temperature and energy homeostasis and provide further insight into the neurochemical regulation of BAT thermogenesis and metabolism
Central Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure
No full textThermogenesis, the production of heat energy, is the specific, neurally regulated, metabolic function of brown adipose tissue (BAT) and contributes to the maintenance of body temperature during cold exposure and to the elevated core temperature during several behavioral states, including wakefulness, the acute phase response (fever), and stress. BAT energy expenditure requires metabolic fuel availability and contributes to energy balance. This review summarizes the functional organization and neurochemical influences within the CNS networks governing the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolically driven alterations in BAT thermogenesis and energy expenditure that contribute to overall energy homeostasis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Central control of brown adipose tissue thermogenesis
No full textThermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. Mitochondrial oxidation in brown adipose tissue (BAT) is a significant source of neurally-regulated metabolic heat production in many species from mouse to man. BAT thermogenesis is regulated by neural networks in the central nervous system which responds to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate BAT sympathetic nerve activity. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates BAT thermogenesis and includes the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature during fever. The cold thermal afferent circuit from cutaneous thermal receptors, through second-order thermosensory neurons in the dorsal horn of the spinal cord ascends to activate neurons in the lateral parabrachial nucleus which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of BAT thermogenesis-promoting neurons in the dorsomedial hypothalamus activates BAT sympathetic premotor neurons in the rostral ventromedial medulla, including the rostral raphe pallidus, which provide excitatory, and possibly disinhibitory, inputs to spinal sympathetic circuits to drive BAT thermogenesis. Other recently recognized central sites influencing BAT thermogenesis and energy expenditure are also described
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