Gut-brain signalling/Bibliography

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Primary Research Papers

Cummings D. (2006) Ghrelin and the short- and long- term regulation of appetite and body weight. Physiology and behaviour 89:71-84 (Ghrelin, an acylated upper gastrointestinal peptide, is the only known orexigenic hormone. Considerable evidence implicates ghrelin in mealtime hunger and meal initiation. Circulating levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Preprandial ghrelin surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues.)

Korbonits M. et al (2004) Ghrelin—a hormone with multiple functions. Frontiers in Neuroendocrinology 25:27-68 (In the current review we comprehensively summarize (i) the data available regarding the structure, expression pattern and regulation of ghrelin and its receptor; (ii) the available information regarding the effect of ghrelin on the pituitary hormone axis, appetite regulation, cardiac and gastrointestinal function, carbohydrate metabolism, adipose and reproductive tissue, cell proliferation and behavioral effects; (iii) experimental and clinical data regarding circulating ghrelin levels observed in various physiological and pathological conditions; and (iv) data on gene variations of ghrelin and its receptor.)

Tsurugizawa T. et al (2009) Mechanisms of Neural Response to Gastrointestinal Nutritive Stimuli: The Gut-Brain Axis. Gastroenterology 137:262-273 (The gut-brain axis, which transmits nutrient information from the gastrointestinal tract to the brain, is important for the detection of dietary nutrients. We used functional magnetic resonance imaging of the rat forebrain to investigate how this pathway conveys nutrient information from the gastrointestinal tract to the brain.)

Guo Z. et al (2008) Different responses of circulating ghrelin, obestatin levels to fasting, re-feeding and different food compositions, and their local expressions in rats. Peptides 29:1247-1254 (Obestatin, a sibling of ghrelin derived from preproghrelin, opposes several physiological actions of ghrelin.)

Kas M.J.H. et al (2005) Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event. Journal of Molecular Endocrinology. 35:159-164 (Neuropeptide Y (NPY) and agouti-related protein (AgRP) are potent food-stimulating neuropeptides that are highly co-localised in arcuate nucleus neurons of the hypothalamus. Recent studies have shown that NPY and AgRP mRNA levels in these neurons respond similarly to fasting and leptin, indicating functional redundancy of the neuropeptide systems in these orexigenic neurons.)

Luquet S. et al (2005) NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates. Science. 310: 683-685 (To determine whether NPY/AgRP neurons are essential in mice, we targeted the human diphtheria toxin receptor to the Agrp locus, which allows temporally controlled ablation of NPY/AgRP neurons to occur after an injection of diphtheria toxin. Neonatal ablation of NPY/AgRP neurons had minimal effects on feeding, whereas their ablation in adults caused rapid starvation.)

Review Papers

Dockray, G. J. (2009) The versatility of the Vagus Physiology & Behaviour 97:531-536 (The gut is one of the several organs contributing to the peripheral signalling network that controls food intake. Afferent neurons of the vagus nerve provide an importnat pathway for gut signals that act by triggering ascending pathways from the brain stem to the hypothalamus.)

Tome, D, Schwarz, J., Darcel, N. and Fromentin, G. (2009) The American Journal of Clinical Nutrition 90:838-43 (At the brain level, 2 afferent pathways are involved in protein and amino acid monitoring: the indirect neural (mainly vagus-mediated) and the direct humoral pathways.)

Näslund E. et al (2007) Appetite signaling: From gut peptides and enteric nerves to brain. Physiology & Behaviour 92:256-262 (The only identified hunger-driving signal from the GI tract is ghrelin, which is mainly found in the mucosa of the stomach. Neuropeptides in the brain that influence food intake, of which neuropeptide Y, agouti gene-related peptide and orexins are stimulatory, while melanocortins and α-melanocortin stimulating hormone are inhibitory, are influenced by peptide signaling from the gut. These effects may take place directly through action of gut peptide in the brain or through nervous signaling from the periphery to the brain. The criteria for considering a gut hormone or neurotransmitter in a satiety signal seem to be fulfilled for cholecystokinin, glucagon-like peptide-1 and peptide YY(3-36).)

Schwartz MW. et al (2000) Central nervous system control of food intake. NATURE 404:661-671 (New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process.)

Druce MR. et al (2004) Minireview: Gut Peptides Regulating Satiety. Endocrinology 145(6):2660-2665 (The gastrointestinal tract and the pancreas release hormones regulating satiety and body weight. Ghrelin stimulates appetite, and glucagon-like peptide-1, oxyntomodulin, peptide YY, cholecystokinin, and pancreatic polypeptide inhibit appetite. These gut hormones act to markedly alter food intake in humans and rodents. Obesity is the current major cause of premature death in the United Kingdom, killing almost 1000 people per week. Worldwide, its prevalence is accelerating. There is currently no effective answer to the pandemic of obesity, but replacement of the low levels of peptideYYobserved in the obese may represent an effective antiobesity therapy.)

Banks WA. (2008) The blood-brain barrier: Connecting the gut and the brain. Regulatory Peptides 149:11-14 (The blood-brain barrier (BBB) also conveys information between the CNS and the gastrointestinal (GI) tract through several mechanisms. Here, we review three of those mechanisms. First, the BBB selectively transports some peptides and regulatory proteins in the blood-to-brain or the brain-to-blood direction. Th ability of GI hormones to affect functions of the BBB, as illustrated by the ability of insulin to alter the BB transport of amino acids and drugs, represents a second mechanism. A third mechanism is the ability of GI hormones to affect the secretion by the BBB of substances that themselves affect feeding and appetite, such as nitric oxide and cytokines.)

Karra E. et al (2009) The role of peptide YY in appetite regulation and obesity. Journal of Physiology 587.1:19-25 (In particular, the discovery that the guthormone peptide YY 3–36 (PYY3–36) reduced feeding in obese rodents and humans fuelled interest in the role of PYY3–36 in body weight regulation. Pharmacological and genetic approaches have revealed that the Y2-receptor mediates the anorectic effects of PYY3–36 whilst mechanistic studies in rodents identified the hypothalamus, vagus and brainstem regions as potential sites of action. More recently, using functional brain imaging techniques in humans, PYY3–36 was found to modulate neuronal activity within hypothalamic and brainstem, and brain regions involved in reward processing. Several lines of evidence suggest that lowcirculating PYY concentrations predispose towards the development and or maintenance of obesity.)

Hameed S. et al (2009) Gut hormones and appetite control. Oral Diseases 15:18-26 (The gastrointestinal tract is the largest endocrine organ in the body. It secretes more than 20 different peptide hormones, which serve both a local regulatory function and provide a means by which the gut can regulate appetite and satiety. As the worldwide prevalence of obesity reaches epidemic proportions, the importance of delineating the mechanisms which regulate food intake becomes even more urgent. There is now a substantial body of work in both rodent and human models demonstrating the effects of these peptides on appetite and work is underway to therapeutically manipulate the gut-brain axis for the treatment of obesity. In addition, it may also be possible to use our understanding of the entero-endocrine system to treat calorie-deficient states.)

Gardiner JV. et al (2008) Gut Hormones: A Weight Off Your Mind. Journal of Neuroendocrinology 20:834-841 (It is well established that the hypothalamus and brain stem are major sites in the central nervous system (CNS) that regulate appetite. Until recently the missing element has been how information regarding food intake and energy stores is communicated to the CNS. Gut hormones have recently been found to be an important element in this regulation, communicating information regarding food intake to the CNS. Several gut hormones have been found to exert anorectic effects. These include members of the Pancreatic Polypeptide (PP)-fold family, namely PP itself and also peptide tyrosine-tyrosine (PYY), the first gut hormone shown to have appetite-inhibiting properties. The other main class of anorectic gut hormones are those derived by proteolytic processing from proglucagon, most importantly glucagon-like peptide-1 (GLP-1) and oxyntomodulin.)

Fink H. et al (1998) Major biological actions of CCK--a critical evaluation of research findings. Exp Brain Res 123:77-83 (Cholecystokinin (CCK) is one of the first discovered gastrointestinal hormones and one of the most abundant neuropeptides in the brain. Two types of CCK receptors have been identified: (1) CCK-A receptors are mainly located in the periphery, but are also found in some areas of the CNS; and (2) CCK-B receptors are widely distributed in the brain. Major biological actions of CCK are the reduction of food intake and the induction of anxiety-related behavior. Inhibition of feeding is mainly mediated by the A-type receptors, whereas anxiety-like behavior is induced by stimulating B-type receptors. This paper presents new findings on the effects of the biologically active CCK agonists, CCK-8S, CCK-4, and A71378...)

Ren A. et al (2009) Obestatin, obesity and diabetes. Peptides 30:439-444 (Obestatin, a novel 23 amino acid amidated peptide encoded by the same gene that encodes ghrelin, was initially reported to have opposite actions to ghrelin in the regulation of food intake, emptying of the stomach and body weight.)

Sheng-Qui T. et all (2008) Obestatin: Its physicochemical characteristics and physiological functions. Peptides 29:639-645 (Obestatin, a novel 23 amino acid amidated peptide encoded by the same gene with ghrelin, was initially reported to reduce food intake, body weight gain, gastric emptying and suppress intestinal motility through an interaction with the orphan receptor GPR39.)

Berthoud H.-R. (2008) Vagal and hormonal gut–brain communication: from satiation to satisfaction. Neurogastroenterol Motil 20:64–72 (Studying communication between the gut and the brain is as relevant and exciting as it has been since Pavlov's discoveries a century ago. Although the efferent limb of this communication has witnessed significant advances, it is the afferent, or sensory, limb that has recently made for exciting news. It is now clear that signals from the gut are crucial for the control of appetite and the regulation of energy balance, glucose homeostasis, and more. Ghrelin, discovered just a few years ago, is the first gut hormone that increases appetite, and it may be involved in eating disorders)

Smith P.M., Ferguson A.V. (2008) Neurophysiology of Hunger and Satiety. Developmental Disabilities Research Reviews. 14: 96 – 104 (Hunger is defined as a strong desire or need for food while satiety is the condition of being full or gratified. The maintenance of energy homeostasis requires a balance between energy intake and energy expenditure. The regulation of food intake is a complex behavior. It requires discrete nuclei within the central nervous system (CNS) to detect signals from the periphery regarding metabolic status, process and integrate this information in a coordinated manner and to provide appropriate responses to ensure that the individual does not enter a state of positive or negative energy balance.