1,720,971 research outputs found
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
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
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
Hibernation, hypothermia and a possible therapeutic "shifted homeostasis" induced by central activation of a1 adenosine receptor (A1AR)
No full textThe positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Pharmacological manipulation of central autonomic thermoregulatory circuits could represent a potential target for the induction of a hypothermic state. Here we present a brief description of the CNS thermoregulatory centers and how the manipulation of these circuits can be useful in the treatment of pathological conditions such as stroke or brain hemorrhage
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
Thermoregulatory Inversion - a novel thermoregulatory paradigm
No full textTo maintain core body temperature in mammals, the normal CNS thermoregulatory reflex networks produce an increase in brown adipose tissue (BAT) thermogenesis in response to skin cooling, and an inhibition of the sympathetic outflow to BAT during skin rewarming. In contrast, these normal thermoregulatory reflexes appear to be inverted in hibernation/torpor: thermogenesis is inhibited during exposure to a cold environment, allowing dramatic reductions in core temperature and metabolism, and thermogenesis is activated during skin rewarming, contributing to a return of normal body temperature. Here we describe two unrelated experimental paradigms in which rats, a non-hibernating/torpid species, exhibit a "Thermoregulatory Inversion", characterized by an inhibition of BAT thermogenesis in response to skin cooling, and a switch in the gain of the skin cooling reflex transfer function from negative to positive values. Either transection of the neuraxis immediately rostral to the dorsomedial hypothalamus in anesthetized rats, or activation of A1 adenosine receptors within the CNS of free-behaving rats produces a state of thermoregulatory inversion, in which skin cooling inhibits BAT thermogenesis, leading to hypothermia, and skin warming activates BAT, supporting an increase in core temperature. These results reflect the existence of a novel neural circuit that mediates inverted thermoregulatory reflexes, and suggests a pharmacologic mechanism through which a deeply hypothermic state can be achieved in non-hibernating/torpid mammals, possibly including humans
Autonomic regulation of brown adipose tissue thermogenesis in health & disease: Potential clinical applications for altering BAT thermogenesis
No full textFrom mouse to man, brown adipose tissue (BAT) is a significant source of thermogenesis contributing to the maintenance of the body temperature homeostasis during the challenge of low environmental temperature. In rodents, BAT thermogenesis also contributes to the febrile increase in core temperature during the immune response. BAT sympathetic nerve activity controlling BAT thermogenesis is regulated by CNS neural networks which respond reflexively to thermal afferent signals from cutaneous and body core thermoreceptors, as well as to alterations in the discharge of central neurons with intrinsic thermosensitivity. Superimposed on the core thermoregulatory circuit for the activation of BAT thermogenesis, is the permissive, modulatory influence of central neural networks controlling metabolic aspects of energy homeostasis. The recent confirmation of the presence of BAT in human and its function as an energy consuming organ have stimulated interest in the potential for the pharmacological activation of BAT to reduce adiposity in the obese. In contrast, the inhibition of BAT thermogenesis could facilitate the induction of therapeutic hypothermia for fever reduction or to improve outcomes in stroke or cardiac ischemia by reducing infarct size through a lowering of metabolic oxygen demand. This review summarizes the central circuits for the autonomic control of BAT thermogenesis and highlights the potential clinical relevance of the pharmacological inhibition or activation of BAT thermogenesis
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
An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis
No full textOrexin (hypocretin) neurons, located exclusively in the PeF-LH, which includes the perifornical area (PeF), the lateral hypothalamus (LH), and lateral portions of the medial hypothalamus, have widespread projections and influence many physiological functions, including the autonomic regulation of body temperature and energy metabolism. Narcolepsy is characterized by the loss of orexin neurons and by disrupted sleep, but also by dysregulation of body temperature and by a strong tendency for obesity. Heat production (thermogenesis) in brown adipose tissue (BAT) contributes to the maintenance of body temperature and, through energy consumption, to body weight regulation. We identified a neural substrate for the influence of orexin neurons on BAT thermogenesis in rat. Nanoinjection of orexin-A (12 pmol) into the rostral raphe pallidus (rRPa), the site of BAT sympathetic premotor neurons, produced large, sustained increases in BAT sympathetic outflow and in BAT thermogenesis. Activation of neurons in the PeF-LH also enhanced BAT thermogenesis over a long time course. Combining viral retrograde tracing from BAT, or cholera toxin subunit b tracing from rRPa, with orexin immunohistochemistry revealed synaptic connections to BAT from orexin neurons in PeF-LH and from rRPa neurons with closely apposed, varicose orexin fibers, as well as a direct, orexinergic projection from PeF-LH to rRPa. These results indicate a potent modulation of BAT thermogenesis by orexin released from the terminals of orexin neurons in PeF-LH directly into the rRPa and provide a potential mechanism contributing to the disrupted regulation of body temperature and energy metabolism in the absence of orexin. � 2011 the authors
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