The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat

Oldfield, Brian J.; Giles, Michelle; Watson, Anna; Anderson, C.R.; Colvill, L M; McKinley, Michael J.

doi:10.1016/s0306-4522(01)00555-3

Cited by 294 publications

(286 citation statements)

References 42 publications

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“…Furthermore, injections of the specific PAC1R agonist maxadilan in the VMN produced the same pattern of behaviors demonstrated by PACAP administration, whereas VIP injections had no effect on either temperature or activity. By contrast, stimulation of the PVN by PACAP did not significantly alter these measures of energy expenditure despite evidence of PVN regulation of sympathetic outflow to BAT (3,46) and its control over the sympathetically driven PACAP-induced glycemic response (60). However, these results are in agreement with reports that PVN neurons inhibit sympathetic activity to BAT (33,37).…”

Section: Discussionsupporting

confidence: 88%

“…Whereas transynaptic retrograde tracing studies from the iBAT often fail to detect VMN neurons (5,46), there is ample evidence supporting VMN activation of BAT thermogenesis, including both VMN-specific microinjection and genetic studies (2,30,49,50). It is feasible that the VMN exerts its influences over hypothalamic structures that are labeled by transynaptic tracers from BAT such as the medial preoptic area, dorsomedial nuclei, or lateral hypothalamus (46,61), allowing for indirect and downstream effects on BAT thermogenesis that are not observed in more proximal polysynaptic tracing experiments. Future studies are needed to reconcile the discrepancy between the anatomical and functional studies regarding VMN-mediated BAT thermogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Resch

Maunze

Gerhardt

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Resch JM, Maunze B, Gerhardt AK, Magnuson SK, Phillips KA, Choi S. Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism. Am J Physiol Endocrinol Metab 305: E1452-E1463, 2013. First published October 22, 2013; doi:10.1152/ajpendo.00293.2013.-Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei, suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites; however, meal pattern analysis revealed that only injections into the PVN produced significant reductions in meal size, duration, and total time spent eating. PACAP-mediated hypophagia in both the PVN and VMN was abolished by PAC1R antagonism, whereas pretreatment with a VPACR antagonist had no effect. PACAP injections into the VMN produced unique changes in metabolic parameters, including significant increases in core body temperature and spontaneous locomotor activity that was PAC1R dependent whereas, PVN injections of PACAP had no effect. Finally, PACAP-containing afferents were identified using the neuronal tracer cholera toxin subunit B (CTB) injected unilaterally into the PVN or VMN. CTB signal from PVN injections was colocalized with PACAP mRNA in the medial anterior bed nucleus of the stria terminalis, VMN, and lateral parabrachial nucleus (LPB), whereas CTB signal from VMN injections was highly colocalized with PACAP mRNA in the medial amygdala and LPB. These brain regions are known to influence energy homeostasis perhaps, in part, through PACAP projections to the PVN and VMN.feeding; activity; temperature; hypothalamus; rat PITUITARY ADENYLATE CYCLASE-ACTIVATING polypeptide (PACAP) is a key regulator of several hypothalamic systems, including stress (1), osmoregulation (17), thermoregulation (21), and body weight (27). PACAP was first discovered to influence energy homeostasis through inhibition of feeding in mice following a single intracerebroventricular (icv) injection of the peptide (39). These results combined with reports of dietspecific alterations of PACAP mRNA expression in the hypothalamic ventromedial nuclei (VMN) suggest that PACAP is responsive to nutritional status and directly tied to metabolic systems linked to energy expenditure (27,40). In addition to reducing food intake, icv administration of PACAP modulates autonomic nerve activity (55) as well as hepatic glucose production (60). As a ligand, PACAP binds to three different G protein-coupled receptors, the PAC1 receptor (PAC1R), and the receptors originally discovered as targets...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Resch

Maunze

Gerhardt

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Since the PVN and ARC express GHS-R1a (Zigman et al 2006), these findings together with our present results may indicate that ghrelin directly activates GHS-R1a in the PVN and ARC and induces a suppressive effect on the sympathetic nervous system innervating BAT. After injection of the neurotropic virus pseudorabies into BAT, infected neurons were present in the PVN, lateral hypothalamus, perifornical region, and retrochiasmatic nucleus (Oldfield et al 2002). A slightly longer survival time for virus-infected neurons appeared in the ARC and dorsomedial hypothalamus (Oldfield et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…After injection of the neurotropic virus pseudorabies into BAT, infected neurons were present in the PVN, lateral hypothalamus, perifornical region, and retrochiasmatic nucleus (Oldfield et al 2002). A slightly longer survival time for virus-infected neurons appeared in the ARC and dorsomedial hypothalamus (Oldfield et al 2002). Another report indicated that raphe pallidus and the PVN were the main areas containing sympathetic premotor neurons activated by cold exposure (Cano et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin suppresses noradrenaline release in the brown adipose tissue of rats

Mano-Otagiri¹,

Ohata²,

Iwasaki-Sekino³

et al. 2009

Journal of Endocrinology

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To clarify the role of ghrelin in the regulatory mechanism of energy metabolism, we analyzed the effects of centrally and peripherally administered ghrelin on noradrenaline release in the brown adipose tissue (BAT) of rats using a microdialysis system. I.c.v. administration of ghrelin at a dose of 500 pmol suppressed noradrenaline release in BAT, and microinjection of ghrelin (50 pmol) into the paraventricular nucleus (PVN) or arcuate nucleus (ARC) of the hypothalamus also suppressed noradrenaline release in BAT. In addition, i.v. administered ghrelin (30 nmol) suppressed noradrenaline release in BAT, and this suppression was blocked by a vagotomy. Neither i.c.v. nor i.v. administration of des-acyl ghrelin, which does not bind to GH secretagogue receptor type 1a (GHS-R1a), affected noradrenaline release in BAT. These results indicate that ghrelin increases energy storage by suppressing the activity of the sympathetic nerve innervating BAT. It seems that the PVN and ARC, which express GHSR1a, are the sites of action of ghrelin in the brain and that the action of peripheral ghrelin on the sympathetic nerve activity innervating BAT is mediated by the vagal nerve, which also expresses GHS-R1a.

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“…By this way, it has been shown that the PVN, the ARC, the nucleus raphe pallidus and raphe obscurus, and the NTS, where cold stress activated a number of nesfatin1/NUCB2-positive cells, are all among the elements of the polysynaptic pathways toward the BAT. 36,37 Moreover, many effects of nesfatin-1 are mediated through melanocortin-3/4 receptors, and the melanocortin-3/4 receptor antagonist SHU9119 significantly decreases BAT temperature. 4,23,38 In addition, prepro-TRH, precursor of TRH, a key factor regulating basal metabolic rate and thermogenesis, co-localised in the cold responsive nesfatin-1/NUCB2 cells in the PVN and in the brainstem raphe nuclei.…”

Section: Discussionmentioning

confidence: 99%

Nesfatin-1 exerts long-term effect on food intake and body temperature

Könczöl

Pintér²,

Ferenczi

et al. 2012

Int J Obes

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OBJECTIVE:To determine whether the anorexigenic peptide, nesfatin-1 affects energy expenditure, and to follow the time course of its effects. DESIGN: Food intake duration, core body temperature, locomotor activity and heart rate of rats were measured by telemetry for 48 h after a single intracerebroventricular injection of 25 or 100 pmol nesfatin-1 applied in the dark or the light phase of the day. Body weight, food and water intake changes were measured daily. Furthermore, cold-responsive nesfatin-1/NUCB2 neurons were mapped in the brain. RESULTS: Nesfatin-1 reduced duration of nocturnal food intake for 2 days independently of circadian time injected, and raised body temperature immediately, or with little delay depending on the dose and circadian time applied. The body temperature remained higher during the next light phases of the 48 h observation period, and the circadian curve of temperature flattened. After light phase application, the heart rate was elevated transiently. Locomotion did not change. Daily food and water intake, as well as body weight measurements point to a potential decrease in all parameters on the first day and some degree of compensation on the second day. Cold-activated (Fos positive) nesfatin-1/NUCB2 neurones have been revealed in several brain nuclei involved in cold adaptation. Nesfatin-1 co-localised with prepro-thyrotropin-releasing hormone in cold responsive neurones of the hypothalamic paraventricular nucleus, and in neurones of the nucleus raphe pallidus and obscurus that are premotor neurones regulating brown adipose tissue thermogenesis and skin blood flow. CONCLUSION: Nesfatin-1 has a remarkably prolonged effect on food intake and body temperature. Time course of nesfatin-1's effects may be varied depending on the time applied. Many of the nesfatin-1/NUCB2 neurones are cold sensitive, and are positioned in key centres of thermoregulation. Nesfatin-1 regulates energy expenditure a far more potent way than it was recognised before making it a preferable candidate anti-obesity drug.

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The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat

Cited by 294 publications

References 42 publications

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

Ghrelin suppresses noradrenaline release in the brown adipose tissue of rats

Nesfatin-1 exerts long-term effect on food intake and body temperature

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