Flipping the tanycyte switch: how circulating signals gain direct access to the metabolic brain

Prevot, Vincent; Langlet, Fanny; Dehouck, Bénédicte

doi:10.18632/aging.100557

Cited by 25 publications

(19 citation statements)

References 9 publications

(19 reference statements)

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“…Further, elegant new studies show that fasting‐induced reduction of blood glucose actually promotes diffusion of blood‐borne metabolic substrates, such as glucose, into the brain through changes in blood vessel fenestration and reorganization of tight junction complexes in the median eminence (Langlet et al ., ). The AP is structurally similar to the median eminence, displaying a network of tanycyte‐like cells and fenestrated capillaries (Langlet et al ., ), and could potentially display similar plasticity during a metabolic challenge like fasting (Prevot et al ., ). If substrate receptivity of the AP does indeed depend on nutritional status, ablation of AP neurons would have clear ramifications on an organism's ability to sense and respond to a metabolic deficit, as we have shown herein.…”

Section: Discussionmentioning

confidence: 97%

The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping

Braegger

Asarian

Dahl³

et al. 2014

Eur J Neurosci

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Amylin reduces meal size by activating noradrenergic neurons in the area postrema (AP). Neurons in the AP also mediate the eating-inhibitory effects of salmon calcitonin (sCT), a potent amylin agonist, but the phenotypes of the neurons mediating its effect are unknown. Here we investigated whether sCT activates similar neuronal populations to amylin, and if its anorectic properties also depend on AP function. Male rats underwent AP lesion (APX) or sham surgery. Meal patterns were analysed under ad libitum and post-deprivation conditions. The importance of the AP in mediating the anorectic action of sCT was examined in feeding experiments of dose-response effects of sCT in APX vs. sham rats. The effect of sCT to induce Fos expression was compared between surgery groups, and relative to amylin. The phenotype of Fos-expressing neurons in the brainstem was examined by testing for the co-expression of dopamine beta hydroxylase (DBH) or tryptophan hydroxylase (TPH). By measuring the apposition of vesicular glutamate transporter-2 (VGLUT2)-positive boutons, potential glutamatergic input to amylinand sCT-activated AP neurons was compared. Similar to amylin, an intact AP was necessary for sCT to reduce eating. Further, co-expression between Fos activation and DBH after amylin or sCT did not differ markedly, while co-localization of Fos and TPH was minor. Approximately 95% of neurons expressing Fos and DBH after amylin or sCT treatment were closely apposed to VGLUT2-positive boutons. Our study suggests that the hindbrain pathways engaged by amylin and sCT share many similarities, including the mediation by AP neurons. AbstractAmylin reduces meal size by activating noradrenergic neurons in the area postrema (AP). Neurons in the AP also mediate the eating-inhibitory effects of salmon calcitonin (sCT), a potent amylin agonist, but the phenotypes of the neurons mediating its effect are unknown. Here we investigated whether sCT activates similar neuronal populations to amylin, and if its anorectic properties also depend on AP function. Male rats underwent AP lesion (APX) or sham surgery. Meal patterns were analysed under ad libitum and post-deprivation conditions. The importance of the AP in mediating the anorectic action of sCT was examined in feeding experiments of dose-response effects of sCT in APX vs. sham rats. The effect of sCT to induce Fos expression was compared between surgery groups, and relative to amylin. The phenotype of Fos-expressing neurons in the brainstem was examined by testing for the co-expression of dopamine beta hydroxylase (DBH) or tryptophan hydroxylase (TPH). By measuring the apposition of vesicular glutamate transporter-2 (VGLUT2)-positive boutons, potential glutamatergic input to amylin-and sCT-activated AP neurons was compared. Similar to amylin, an intact AP was necessary for sCT to reduce eating. Further, co-expression between Fos activation and DBH after amylin or sCT did not differ markedly, while co-localization of Fos and TPH was minor. Approximately 95% of neurons expressing Fos...

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Section: Discussionmentioning

confidence: 97%

The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping

Braegger

Asarian

Dahl³

et al. 2014

Eur J Neurosci

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“…Most importantly, our study also indicated that ghrelin signaling can be modulated, at least under certain physiological conditions in ewes, by the serotonin receptor agonist m-CPP. In a recent study, Prevot et al [23] established a new physiological concept in the regulation of energy homeostasis by demonstrating that the nutritional status of an individual modulates the permeability of discrete blood hypothalamus barriers to circulating metabolic signals, thereby permitting them to directly access a subset of hypothalamic neurons. In seasonal breeding ewes, the photoperiodic signal melatonin, a lipophilic molecule, can easily penetrate the cerebrospinal fluid (CSF).…”

Section: Discussionmentioning

confidence: 99%

Photoperiod Influences the Effects of Ghrelin and Serotonin Receptor Agonist on Growth Hormone and Prolactin Secretion in Sheep

Zieba¹,

Kirsz²,

Szczesna³

et al. 2015

J Neurol Neurophysiol

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Objective: Recent studies have identified a novel heterodimer involving the ghrelin receptor (GHS-R1A) and the 5-HT2C receptor, a subtype of serotonin receptors. Whether or not interactions between GHS-R1A and the 5-HT2C receptor exist and how they are modulated by photoperiod and nutritional status in seasonally animals remains unknown. The aims of this study were to determine the effects of ghrelin and a 5-HT2B/2C serotonin receptor agonist, 1-(3-chlorophenyl) piperazine hydrochloride (m-CPP), on GH and PRL secretion under the influence of nutritional status and photoperiod.Methods: Normally fed (n=12) or fasted (n=12) ewes were assigned to one of 4 groups and treatments: 1) control (saline); 2) ghrelin (2.5 μg/kg); 3) m-CPP (2.5 mg/kg); 4) ghrelin followed by m-CPP were infused once at the beginning of the study for groups 1, 2 and 3; in group 4, ghrelin was administered at 15 min, and m-CPP at 30 min. Blood samples were collected at 15-min intervals for 3 h during the short day (SD) and long day (LD) season.Results: Ghrelin and m-CPP enhanced (p<0.05) GH secretion in fasted ewes during LD. The m-CPP significantly decreased GH concentrations in fasted ewes during SD. Prolactin concentrations were lower (p<0.01) in normally fed ewes after the ghrelin + m-CPP treatment compared to treatment with m-CPP alone. Conclusion:There were interactions among ghrelin, serotonin, photoperiod and metabolic status that influenced GH and PRL secretion in ewes. Using an ovine model, our work provides a basis for future studies of the pathogenesis of metabolic disorders associated with alterations in nutritional status and day length.

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“…It is the neurones of the ARC that rapidly respond with AKT Ser‐473 phosphorylation, a surrogate marker of IR activation, and c‐Fos, a surrogate marker of neuronal activation, in response to a peripheral bolus of insulin; this effect is attenuated in insulin‐resistant states such as T2D and obesity . The restriction of the capillary fenestration to the ME together with the presence of tight junction complexes between adjacent tanycytes (specialised hypothalamic glia that line the third ventricle and extend processes to contact the capillary plexus) acts as a physical barrier controlling the diffusion of hormones such as insulin to the rest of the brain interstitial fluid (ISF) . There is some evidence suggesting that the capillary loops reaching the ARC can be affected by nutritional state .…”

Section: Insulin Transportmentioning

confidence: 99%

“…[18][19][20][21][22][23] The restriction of the capillary fenestration to the ME together with the presence of tight junction complexes between adjacent tanycytes (specialised hypothalamic glia that line the third ventricle and extend processes to contact the capillary plexus) acts as a physical barrier controlling the diffusion of hormones such as insulin to the rest of the brain interstitial fluid (ISF). [24][25][26] There is some evidence suggesting that the capillary loops reaching the ARC can be affected by nutritional state. 26,27 In addition, studies attempting to measure ARC ISF by microdialysis show that the low levels of fasting concentrations of insulin in the ARC are rapidly increased 30 minutes after feeding or peripheral insulin infusion.…”

Section: Cns Entry Via the Median Eminencementioning

confidence: 99%

Insulin action in the brain: Roles in energy and glucose homeostasis

Dodd

Tiganis

2017

J Neuroendocrinol

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A growing body of evidence from research in rodents and humans has identified insulin as an important neuoregulatory peptide in the brain, where it coordinates diverse aspects of energy balance and peripheral glucose homeostasis. This review discusses where and how insulin interacts within the brain and evaluates the physiological and pathophysiological consequences of central insulin signalling in metabolism, obesity and type 2 diabetes. K E Y W O R D SAgRP, energy homeostasis, glucose homeostasis, hypothalamus, insulin, POMC | INTRODUCTIONInsulin targets peripheral tissues, including skeletal muscle, adipose tissue, where it promotes glucose uptake from the blood, and the liver, where it inhibits gluconeogenesis and glycogenolysis and promotes glycogen synthesis to coordinately repress hepatic glucose production.In this way, insulin prevents postprandial hyperglycaemia and maintains euglycaemia. In addition to these peripheral targets, insulin also signals in the brain, although the physiological significance of this interaction has only recently started to emerge. Research over the past two decades has provided compelling evidence that central insulin signalling plays pivotal roles in many aspects of energy and glucose homeostasis (Figure 1). Given the epidemics of obesity and type 2 diabetes (T2D) in developed and increasingly developing countries, there is a pressing need to fully understand the mechanisms by which the body coordinates energy and glucose homeostasis. A key hallmark of obesity and T2D is insulin resistance, where defective insulin signalling downstream of the insulin receptor (IR) renders the peripheral target tissues of insulin insensitive to the action of insulin. What is becoming increasingly apparent is that neurones in the brain also become resistant to insulin; however the relative contributions of central insulin resistance to the development of obesity and T2D remain poorly understood.This review discusses the role of insulin in the brain with respect to coordinating glucose metabolism with energy expenditure. In particular, we discuss our understanding of the locations and mechanisms by which insulin elicits its effects in the brain, its influence on glucose metabolism and energy expenditure, and the potential contributions of central insulin resistancein the development of obesity and the metabolic syndrome.

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Flipping the tanycyte switch: how circulating signals gain direct access to the metabolic brain

Cited by 25 publications

References 9 publications

The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping

The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping

Photoperiod Influences the Effects of Ghrelin and Serotonin Receptor Agonist on Growth Hormone and Prolactin Secretion in Sheep

Insulin action in the brain: Roles in energy and glucose homeostasis

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