Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus

Akieda-Asai, Sayaka; Poleni, Paul-Emile; Date, Yukari

doi:10.1152/ajpendo.00664.2013

Cited by 42 publications

(17 citation statements)

References 56 publications

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“…Although no longevity studies have been conducted with exogenously delivered CCK, it is therefore likely that CCK activates PI3K/Akt/mTOR signaling. However, CCK also acts synergistically with leptin to promote satiety, possibly by activating AMPK in the hypothalamus (Akieda-Asai et al 2014 ), which may inhibit mTORC1 signaling. It therefore appears likely that the context in which CCK activation takes place may be important in understanding its effect on PI3K/Akt/mTOR activity.…”

Section: Reviewmentioning

confidence: 99%

Diminished mTOR signaling: a common mode of action for endocrine longevity factors

Lamming

2014

SpringerPlus

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Since the initial observation that a calorie-restricted (CR) diet can extend rodent lifespan, many genetic and pharmaceutical interventions that also extend lifespan in mammals have been discovered. The mechanism by which CR and these other interventions extend lifespan is the subject of significant debate and research. One proposed mechanism is that CR promotes longevity by increasing insulin sensitivity, but recent findings that dissociate longevity and insulin sensitivity cast doubt on this hypothesis. These findings can be reconciled if longevity is promoted not via increased insulin sensitivity, but instead via decreased PI3K/Akt/mTOR pathway signaling. This review presents a unifying hypothesis that explains the lifespan-extending effects of a variety of genetic mutations and pharmaceutical interventions and points towards new molecular pathways which may also be leveraged to promote healthy aging.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-735) contains supplementary material, which is available to authorized users.

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Section: Reviewmentioning

confidence: 99%

Diminished mTOR signaling: a common mode of action for endocrine longevity factors

Lamming

2014

SpringerPlus

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“…Recently, it was reported that co‐administration of subthreshold GLP‐1 or CCK and leptin significantly reduces feeding in rats . GLP‐1 or CCK and leptin cooperatively reduce feeding at least in part via inhibition of AMPK after driving the neural circuits of the hypothalamus following the integration of these anorectic signals in the brain stem and transporting them to the hypothalamus . However, the effect of simultaneous i.p.…”

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confidence: 99%

Activation of Nesfatin‐1‐Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin‐1 in Rats

Saito

Motojima

et al. 2016

J Neuroendocrinology

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Peripheral anorectic hormones, such as glucagon-like peptide (GLP)-1, cholecystokinin (CCK)-8 and leptin, suppress food intake. The newly-identified anorectic neuropeptide, nesfatin-1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP-1 and CCK-8 and co-administrations of GLP-1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin-1-immunoreactive (-IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP-1 (100 μg/kg) caused significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK-8 (50 μg/kg) resulted in marked increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP-1 (33 μg/kg) or leptin. However, co-administration of GLP-1 (33 μg/kg) and leptin resulted in significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP-1, CCK-8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin-1. These results indicate that nesfatin-1-expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP-1 and leptin in addition to CCK-8, and also suppress food intake in rats.

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“…Central administration of TRH or TRH agonists consistently reduces food intake in normal rodents and hungry rats, and in models of stress-induced feeding increases thermogenesis and arousal (Lechan & Fekete 2006, Akieda-Asai et al 2014. These effects may involve various hypothalamic targets because, for example, local injection of TRH into medial and lateral hypothalamus (LH) reduces feeding in rats (Suzuki et al 1982) whereas administration into the preoptic area, dorsomedial, or ventromedial hypothalamus (VMH) increases BAT temperature in hamsters (Shintani et al 2005).…”

Section: Hypothalamic Trh Neuronal Populationsmentioning

confidence: 99%

Regulation of TRH neurons and energy homeostasis-related signals under stress

Joseph‐Bravo

Jaimes-Hoy

Charlí

2015

Journal of Endocrinology

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Energy homeostasis relies on a concerted response of the nervous and endocrine systems to signals evoked by intake, storage, and expenditure of fuels. Glucocorticoids (GCs) and thyroid hormones are involved in meeting immediate energy demands, thus placing the hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-adrenal axes at a central interface. This review describes the mode of regulation of hypophysiotropic TRHergic neurons and the evidence supporting the concept that they act as metabolic integrators. Emphasis has been be placed on i) the effects of GCs on the modulation of transcription of Trh in vivo and in vitro, ii) the physiological and molecular mechanisms by which acute or chronic situations of stress and energy demands affect the activity of TRHergic neurons and the HPT axis, and iii) the less explored role of non-hypophysiotropic hypothalamic TRH neurons. The partial evidence gathered so far is indicative of a contrasting involvement of distinct TRH cell types, manifested through variability in cellular phenotype and physiology, including rapid responses to energy demands for thermogenesis or physical activity and nutritional status that may be modified according to stress history.

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Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus

Cited by 42 publications

References 56 publications

Diminished mTOR signaling: a common mode of action for endocrine longevity factors

Diminished mTOR signaling: a common mode of action for endocrine longevity factors

Activation of Nesfatin‐1‐Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin‐1 in Rats

Regulation of TRH neurons and energy homeostasis-related signals under stress

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