Journal ArticleDOI
Gut hormone PYY 3-36 physiologically inhibits food intake
Rachel L. Batterham,Michael A. Cowley,Caroline J. Small,Herbert Herzog,Mark Cohen,C. L. Dakin,Alison M. Wren,Audrey E. Brynes,Malcolm J. Low,Mohammad A. Ghatei,Roger D. Cone,Stephen R. Bloom +11 more
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TLDR
In this paper, the authors showed that post-prandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.Abstract:
Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus(1). The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons(2) in the arcuate nucleus, which is accessible to peripheral hormones(3). Peptide YY3-36 (PYY3-36), a Y2R agonist(4), is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal(5-7). Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons(8). In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.read more
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The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism
Gijs den Besten,Karen van Eunen,Albert K. Groen,Koen Venema,Dirk-Jan Reijngoud,Barbara M. Bakker +5 more
TL;DR: This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism.
Journal ArticleDOI
Central nervous system control of food intake and body weight
TL;DR: This new information provides a biological context within which to consider the global obesity epidemic and identifies numerous potential avenues for therapeutic intervention and future research.
Journal ArticleDOI
Inhibition of food intake in obese subjects by peptide YY3-36.
Rachel L. Batterham,Mark Cohen,Sandra M. Ellis,Carel W. le Roux,Dominic J. Withers,Gary Frost,Mohammad A. Ghatei,Stephen R. Bloom +7 more
TL;DR: It is found that obese subjects were not resistant to the anorectic effects of PYY, and endogenous PYY levels were low in obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.
Journal ArticleDOI
The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
Michael A. Cowley,Roy G. Smith,Sabrina Diano,Matthias H. Tschöp,Nina Pronchuk,Kevin L. Grove,Christian J. Strasburger,Martin Bidlingmaier,Michael Esterman,Mark L. Heiman,Luis M. Garcia-Segura,Eduardo A. Nillni,Pablo Mendez,Malcolm J. Low,Péter Sótonyi,Jeffrey M. Friedman,Hongyan Liu,Shirly Pinto,William F. Colmers,Roger D. Cone,Tamas L. Horvath +20 more
TL;DR: Using electrophysiological recordings, ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH), thus representing a novel regulatory circuit controlling energy homeostasis.
Journal ArticleDOI
PPARs and the complex journey to obesity
TL;DR: The elucidation of key regulators of energy balance and insulin signaling have revolutionized understanding of fat and sugar metabolism and their intimate link, and the three 'lipid-sensing' peroxisome proliferator–activated receptors exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis.
References
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Book
The Mouse Brain in Stereotaxic Coordinates
TL;DR: The 3rd edition of this atlas is now in more practical 14"x11" format for convenient lab use and includes a CD of all plates and diagrams, as well as Adobe Illustrator files of the diagrams, and a variety of additional useful material.
Journal ArticleDOI
Central nervous system control of food intake
TL;DR: A model is described that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.
Journal ArticleDOI
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Michael A. Cowley,James L. Smart,Marcelo Rubinstein,Marcelo G. Cerdán,Sabrina Diano,Tamas L. Horvath,Roger D. Cone,Malcolm J. Low +7 more
TL;DR: An integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus is proposed and it is shown that melanocortin peptides have an autoinhibitory effect on this circuit.
Journal ArticleDOI
Interacting appetite-regulating pathways in the hypothalamic regulation of body weight.
TL;DR: Multiple orexigenic and anorexigenic pathways in the hypothalamic ARN appear to represent redundancy, a characteristic of regulated biological systems to provide a "fail-safe" neural mechanism to meet an organism's constant energy needs for growth and maintenance.
Journal ArticleDOI
Human distribution and release of a putative new gut hormone, peptide YY
Thomas E. Adrian,Gian-Luca Ferri,A J Bacarese-Hamilton,H.S. Fuessl,J M Polak,Stephen R. Bloom +5 more
TL;DR: The known potent biologic actions of PYY, its high concentrations in gut endocrine cells, and its release into the circulation after a normal meal suggest that this peptide may function physiologically as a circulating gut hormone.