The sensitivity of AP neurons to amylin and GLP-1 is modulated by the feeding status

Züger, Daniela; K, Forster; Lutz, Thomas; Riediger, Thomas

doi:10.1016/j.appet.2011.05.303

Cited by 2 publications

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“…While blood glucose levels were also similar, blood amino acid levels decreased in rats fed low-protein diet suggesting that circulating amino acids might contribute the protein-dependent attenuation of amylin-induced AP activation. Pre-treatment of rats with an intraperitoneal administration of a mixed amino acid solution also attenuated amylin's c-Fos response in the AP, which supports this hypothesis (149) . However, the exact neuronal mechanism underlying the protein-dependent modulation of amylin signalling remains to be identified.…”

Section: Interaction Of Amylin and Nutrient Signallingsupporting

confidence: 76%

“…Amylin more potently decreased intake of 1 and 8% protein chow than standard chow containing 18% protein. Similarly, amylin-induced c-Fos expression was higher in rats receiving less protein ( 149 ) . These effects were not secondary to altered energy intake that was similar across the experimental groups.…”

Section: The Area Postremamentioning

confidence: 99%

“…Although amylin and GLP-1 activate AP neurons, these hormones seem to have different target cells in the AP. Similar to the aversive stimulus lithium chloride, GLP-1 and exendin-4 almost exclusively activate AP neurons that do not express the calcitonin receptor, which is considered as a marker for the primary target cells for amylin in the AP (149) . The functional implication of this dissociation has not yet been specifically investigated.…”

Section: Hormonal Interactions Involving Area Postrema and Brainstem mentioning

confidence: 99%

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The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

Riediger

2012

Proc. Nutr. Soc.

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The hypothalamic arcuate nucleus (ARC) and the area postrema (AP) represent targets for hormonal and metabolic signals involved in energy homoeostasis, e.g. glucose, amylin, insulin, leptin, peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and ghrelin. Orexigenic neuropeptide Y expressing ARC neurons are activated by food deprivation and inhibited by feeding in a nutrient-dependent manner. PYY and leptin also reverse or prevent fasting-induced activation of the ARC. Interestingly, hypothalamic responses to fasting are blunted in different models of obesity (e.g. diet-induced obesity (DIO) or late-onset obesity). The AP also responds to feeding-related signals. The pancreatic hormone amylin acts via the AP to control energy intake. Amylin-sensitive AP neurons are also glucose-responsive. Furthermore, diet-derived protein attenuates amylin responsiveness suggesting a modulation of AP sensitivity by macronutrient supply. This review gives an overview of the receptive function of the ARC and the AP to hormonal and nutritional stimuli involved in the control of energy balance and the possible implications in the context of obesity. Collectively, there is consistency between the neurophysiological actions of these stimuli and their effects on energy homoeostasis under experimental conditions. However, surprisingly little progress has been made in the development of effective pharmacological approaches against obesity. A promising way to improve effectiveness involves combination treatments (e.g. amylin/leptin agonists). Hormonal alterations (e.g. GLP-1 and PYY) are also considered to mediate body weight loss observed in obese patients receiving bariatric surgery. The effects of hormonal and nutritional signals and their interactions might hold the potential to develop poly-mechanistic therapeutic strategies against obesity. Arcuate nucleus: Area postrema: Food intake: ObesityDriven by the search for therapeutic treatment strategies against obesity and associated metabolic disorders, considerable knowledge has accumulated about the control mechanisms involved in the maintenance of energy balance. The redundancy of control mechanisms, the capacity of these systems to compensate for pharmacological effects and the existence of obesity-related hormonal insensitivities make it difficult to achieve sufficient therapeutic efficiency for the reduction of body weight over longer periods of time. Evidently, at least under nonlaboratory conditions, so-called non-homoeostatic factors (hedonic properties and availability of food, food preferences, social factors, eating habits, etc.) and central reward mechanisms override homoeostatic hormonal and metabolic signals that are considered to reflect and to control the body's energy status.

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Section: Interaction Of Amylin and Nutrient Signallingsupporting

confidence: 76%

Section: The Area Postremamentioning

confidence: 99%

Section: Hormonal Interactions Involving Area Postrema and Brainstem mentioning

confidence: 99%

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The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

Riediger

2012

Proc. Nutr. Soc.

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Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

Potes

Boyle

Wookey

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Potes CS, Boyle CN, Wookey PJ, Riediger T, Lutz TA. Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect. Am J Physiol Regul Integr Comp Physiol 302: R340 -R351, 2012. First published November 30, 2011 doi:10.1152/ajpregu.00380.2011.-Peripheral amylin inhibits eating via the area postrema (AP). Because amylin activates the extracellular-signal regulated kinase 1/2 (ERK) pathway in some tissues, and because ERK1/2 phosphorylation (pERK) leads to acute neuronal responses, we postulated that it may be involved in amylin's eating inhibitory effect. Amylin-induced ERK phosphorylation (pERK) was investigated by immunohistochemistry in brain sections containing the AP. pERK-positive AP neurons were double-stained for the calcitonin 1a/b receptor, which is part of the functional amylin-receptor. AP sections were also phenotyped using dopamine-␤-hydroxylase (DBH) as a marker of noradrenergic neurons. The effect of fourth ventricular administration of the ERK cascade blocker U0126 on amylin's eating inhibitory action was tested in feeding trials. The number of pERK-positive neurons in the AP was highest ϳ10 -15 min after amylin treatment; the effect appeared to be dosedependent (5-20 g/kg amylin). A portion of pERK-positive neurons in the AP carried the amylin-receptor and 22% of the pERK-positive neurons were noradrenergic. Pretreatment of rats with U0126 decreased the number of pERK-positive neurons in the AP after amylin injection. U0126 also attenuated the ability of amylin to reduce eating, at least when the animals had been fasted 24 h prior to the feeding trial. Overall, our results suggest that amylin directly stimulates pERK in AP neurons in a time-and dose-dependent manner. Part of the AP neurons displaying pERK were noradrenergic. At least under fasting conditions, pERK was shown to be a necessary part in the signaling cascade mediating amylin's anorectic effect.ERK; MAPK; area postrema; amylin receptor; U0126 THE HOMEOSTATIC SYSTEM CONTROLLING food intake and body weight relies to a large extent on peripheral satiation signals.One of these signals is amylin, a peptide cosecreted with insulin by pancreatic ␤-cells in response to nutrient ingestion (12, 41). At near-physiological plasma concentrations, amylin effectively decreases food intake in rats, and is considered a physiological satiation signal (4, 27). The amylin analog pramlintide causes weight loss in obese humans that is accompanied by sustained reductions in 24-h food intake, portion sizes, fast food intake, and binge eating tendencies (5, 57).Pharmacological and lesioning studies implicate the area postrema (AP) as the primary site of amylin's anorectic action (29,30,35), and an excitatory action of amylin on AP neurons has been confirmed by electrophysiological studies (49). Immunohistochemical studies using the immediate early gene product c-Fos as a marker of neuronal activation showed that peripheral amylin activates the AP, and subsequently the nucleus of the solitary tract (NTS),...

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The sensitivity of AP neurons to amylin and GLP-1 is modulated by the feeding status

Cited by 2 publications

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The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

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