The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

Author(s): Yi Wu, Hengxun He, Zhibin Cheng*, Yueyu Bai*, Xi Ma*.

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 7 , 2019

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Graphical Abstract:


Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

Keywords: Gut-brain axis, obesity, neuropeptide Y, peptide YY, brain-gut peptide, gut microbiota.

World Health Organization. Global Health Risks., (Accessed September 24, 2014).
Nie, C.; He, T.; Zhang, W.; Zhang, G.; Ma, X. Branched chain amino acids: Beyond nutrition metabolism. Int. J. Mol. Sci., 2018, 19, 954.
Cefalu, W.T.; Bray, G.A.; Home, P.D.; Garvey, W.T.; Klein, S.; Pi-Sunyer, F.X.; Hu, F.B.; Raz, I.; Van Gaal, L.; Wolfe, B.M.; Ryan, D.H. Advances in the science, treatment, and prevention of the disease of obesity: Reflections from a diabetes care editors’ expert forum. Diabetes Care, 2015, 38, 1567-1582.
Ma, X.; Ding, W.; Wang, J.; Wu, G.; Zhang, H.; Yin, J.; Zhou, L.; Li, D. LOC66273 isoform 2, a novel protein highly expressed in white adipose tissue, induces adipogenesis in 3T3-L1 cells. J. Nutr., 2012, 142, 448-455.
Ma, X. Signal proteins involved in glucose and lipid metabolism regulation. Curr. Protein Pept. Sci., 2017, 18, 524.
Hu, S.; Han, M.; Rezaei, A.; Li, D.; Wu, G.; Ma, X. L-arginine modulates glucose and lipid metabolism in obesity and diabetes. Curr. Protein Pept. Sci., 2017, 18, 599-608.
Ionut, V.; Burch, M.; Youdim, A.; Bergman, R.N. Gastrointestinal hormones and bariatric surgery-induced weight loss. Obesity (Silver Spring), 2013, 21, 1093-1103.
Tamboli, R.A.; Antoun, J.; Sidani, R.M.; Clements, A.; Harmata, E.E.; Marks-Shulman, P.; Gaylinn, B.D.; Williams, B.; Clements, R.H.; Albaugh, V.L.; Abumrad, N.N. Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans. Diabetes Obes. Metab., 2017, 19, 1267-1275.
Manning, S.; Pucci, A.; Batterham, R.L. Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms. J. Clin. Invest., 2015, 125, 939-948.
Yanovski, S.Z.; Yanovski, J.A. Long-term drug treatment for obesity: a systematic and clinical review. JAMA, 2014, 311, 74-86.
Hall, J.E.; do Carmo, J.M.; da Silva, A.A.; Wang, Z.; Hall, M.E. Obesity-induced hypertension: Interaction of neurohumoral and renal mechanisms. Circ. Res., 2015, 116, 991-1006.
Lee, E.B.; Mattson, M.P. The neuropathology of obesity: Insights from human disease. Acta Neuropathol., 2014, 127, 3-28.
Ueno, H.; Nakazato, M. Mechanistic relationship between the vagal afferent pathway, central nervous system and peripheral organs in appetite regulation. J. Diabetes Investig., 2016, 7, 812-818.
Banks, W.A. Evidence for a cholecystokinin gut-brain axis with modulation by bombesin. Peptides, 1980, 1, 347-351.
Latorre, R.; Sternini, C.; De Giorgio, R.; Greenwood-Van Meerveld, B. Enteroendocrine cells: A review of their role in brain-gut communication. Neurogastroenterol. Motil., 2016, 28, 620-630.
Mayer, E.A. Gut feelings: The emerging biology of gut-brain communication. Nat. Rev. Neurosci., 2011, 12, 453-466.
Guarino, D.; Nannipieri, M.; Iervasi, G.; Taddei, S.; Bruno, R.M. The role of the autonomic nervous system in the pathophysiology of obesity. Front. Physiol., 2017, 8, 665.
Newgreen, D.F.; Dufour, S.; Howard, M.J.; Landman, K.A. Simple rules for a “simple” nervous system? Molecular and biomathematical approaches to enteric nervous system formation and malformation. Dev. Biol., 2013, 382, 305-319.
Chandrasekharan, B.; Srinivasan, S. Diabetes and the enteric nervous system. Neurogastroenterol. Motil., 2007, 19, 951-960.
Carabotti, M.; Scirocco, A.; Maselli, M.A.; Severi, C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol., 2015, 28, 203-209.
Baudry, C.; Reichardt, F.; Marchix, J.; Bado, A.; Schemann, M.; des Varannes, S.B.; Neunlist, M.; Moriez, R. Diet-induced obesity has neuroprotective effects in murine gastric enteric nervous system: Involvement of leptin and glial cell line-derived neurotrophic factor. J. Physiol., 2012, 590, 533-544.
Agustí, A.; García-Pardo, M.P.; López-Almela, I.; Campillo, I.; Maes, M.; Romaní-Pérez, M.; Sanz, Y. Interplay between the gut-brain axis, obesity and cognitive function. Front. Neurosci., 2018, 12, 155.
Adamska, E.; Ostrowska, L.; Górska, M.; Krętowski, A. The role of gastrointestinal hormones in the pathogenesis of obesity and type 2 diabetes. Prz. Gastroenterol., 2014, 9, 69-76.
Alamshah, A.; McGavigan, A.K.; Spreckley, E.; Kinsey-Jones, J.S.; Amin, A.; Tough, I.R.; O’Hara, H.C.; Moolla, A.; Banks, K.; France, R.; Hyberg, G.; Norton, M.; Cheong, W.; Lehmann, A.; Bloom, S.R.; Cox, H.M.; Murphy, K.G. L-arginine promotes gut hormone release and reduces food intake in rodents. Diabetes Obes. Metab., 2016, 18, 508-518.
Ma, N.; Guo, P.; Zhang, J.; He, T.; Kim, S.W.; Zhang, G.; Ma, X. Nutrients mediate intestinal bacteria-mucosal immune crosstalk. Front. Immunol., 2018, 9, 5.
Liu, H.; Wang, J.; He, T.; Becker, S.; Zhang, G.; Li, D.; Ma, X. Butyrate: A double-edged sword for health? Adv. Nutr., 2018, 9, 21-29.
Magkos, F.; Fraterrigo, G.; Yoshino, J.; Luecking, C.; Kirbach, K.; Kelly, S.C.; de Las Fuentes, L.; He, S.; Okunade, A.L.; Patterson, B.W.; Klein, S. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab., 2016, 23, 591-601.
Clemmensen, C.; Müller, T.D.; Woods, S.C.; Berthoud, H.R.; Seeley, R.J.; Tschöp, M.H. Gut-brain cross-talk in metabolic control. Cell, 2017, 168, 758-774.
Fan, P.; Li, L.; Rezaei, A.; Eslamfam, S.; Che, D.; Ma, X. Metabolites of dietary protein and peptides by intestinal microbes and their impacts on gut. Curr. Protein Pept. Sci., 2015, 16, 646-654.
Tan, T.; Behary, P.; Tharakan, G.; Minnion, J.; Al-Najim, W.; Albrechtsen, N.J.W.; Holst, J.J.; Bloom, S.R. The effect of a subcutaneous infusion of GLP-1, OXM, and PYY on energy intake and expenditure in obese volunteers. J. Clin. Endocrinol. Metab., 2017, 102, 2364-2372.
Iepsen, E.W.; Zhang, J.; Thomsen, H.S.; Hansen, E.L.; Hollensted, M.; Madsbad, S.; Hansen, T.; Holst, J.J.; Holm, J.C.; Torekov, S.S. Patients with obesity caused by melanocortin-4 receptor mutations can be treated with a glucagon-like peptide-1 receptor agonist. Cell Metab., 2018, 28, 23-32.
Stephens, R.W.; Arhire, L.; Covasa, M. Gut microbiota: From microorganisms to metabolic organ influencing obesity. Obesity (Silver Spring), 2018, 26, 801-809.
Bauer, P.V.; Hamr, S.C.; Duca, F.A. Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota. Cell. Mol. Life Sci., 2016, 73, 737-755.
van de Wouw, M.; Schellekens, H.; Dinan, T.G.; Cryan, J.F. Microbiota-gut-brain axis: modulator of host metabolism and appetite. J. Nutr., 2017, 147, 727-745.
Priyadarshini, M.; Wicksteed, B.; Schiltz, G.E.; Gilchrist, A.; Layden, B.T. SCFA receptors in pancreatic β cells: Novel diabetes targets? Trends Endocrinol. Metab., 2016, 27, 653-664.
Tang, C.; Offermanns, S. FFA2 and FFA3 in metabolic regulation. Handb. Exp. Pharmacol., 2017, 236, 205-220.
Breton, J.; Tennoune, N.; Lucas, N.; Francois, M.; Legrand, R.; Jacquemot, J.; Goichon, A.; Guérin, C.; Peltier, J.; Pestel-Caron, M.; Chan, P.; Vaudry, D.; do Rego, J.C.; Liénard, F.; Pénicaud, L.; Fioramonti, X.; Ebenezer, I.S.; Hökfelt, T.; Déchelotte, P.; Fetissov, S.O. Gut commensal e. coli proteins activate host satiety pathways following nutrient-induced bacterial growth. Cell Metab., 2016, 23, 324-334.
Perry, R.J.; Peng, L.; Barry, N.A.; Cline, G.W.; Zhang, D.; Cardone, R.L.; Petersen, K.F.; Kibbey, R.G.; Goodman, A.L.; Shulman, G.I. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature, 2016, 534, 213-217.
Kanoski, S.E.; Hayes, M.R.; Skibicka, K.P. GLP-1 and weight loss: Unraveling the diverse neural circuitry. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2016, 310, R885-R895.
Dailey, M.J.; Moran, T.H. Glucagon-like peptide 1 and appetite. Trends Endocrinol. Metab., 2013, 24, 85-91.
Narayanaswami, V.; Dwoskin, L.P. Obesity: Current and potential pharmacotherapeutics and targets. Pharmacol. Ther., 2017, 170, 116-147.
Huang, T.; Zheng, Y.; Hruby, A.; Williamson, D.A.; Bray, G.A.; Shen, Y.; Sacks, F.M.; Qi, L. Dietary protein modifies the effect of the MC4R genotype on 2-year changes in appetite and food craving: The POUNDS lost trial. J. Nutr., 2017, 147, 439-444.
Painchaud Guérard, G. Lemieux, S1.; Doucet, É.; Pomerleau, S.; Provencher, V. Influence of nutrition claims on appetite sensations according to sex, weight status, and restrained eating. J. Obes., 2016, 20169475476
Liedtke, W.B.; McKinley, M.J.; Walker, L.L.; Zhang, H.; Pfenning, A.R.; Drago, J.; Hochendoner, S.J.; Hilton, D.L.; Lawrence, A.J.; Denton, D.A. Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite. Proc. Natl. Acad. Sci. USA, 2011, 108, 12509-12514.
D’Agostino, G.; Lyons, D.J.; Cristiano, C.; Burke, L.K.; Madara, J.C.; Campbell, J.N.; Garcia, A.P.; Land, B.B.; Lowell, B.B.; Dileone, R.J.; Heisler, L.K. Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. eLife, 2016, 5e12225
Fan, P.; Liu, P.; Song, P.; Chen, X.; Ma, X. Moderate dietary protein restriction alters the composition of gut microbiota and improves ileal barrier function in adult pig model. Sci. Rep., 2017, 7, 43412.
Bi, S.; Kim, Y.J.; Zheng, F. Dorsomedial hypothalamic NPY and energy balance control. Neuropeptides, 2012, 46, 309-314.
Bliss, E.S.; Whiteside, E. The gut-brain axis, the human gut microbiota and their integration in the development of obesity. Front. Physiol., 2018, 9, 900.
Loh, K.; Zhang, L.; Brandon, A.; Wang, Q.; Begg, D.; Qi, Y.; Fu, M.; Kulkarni, R.; Teo, J.; Baldock, P.; Brüning, J.C.; Cooney, G.; Neely, G.; Herzog, H. Insulin controls food intake and energy balance via NPY neurons. Mol. Metab., 2017, 6, 574-584.
Macarthur, H.; Wilken, G.H.; Westfall, T.C.; Kolo, L.L. Neuronal and non-neuronal modulation of sympathetic neurovascular transmission. Acta Physiol. (Oxf.), 2011, 203, 37-45.
Toneff, T.; Funkelstein, L.; Mosier, C.; Abagyan, A.; Ziegler, M.; Hook, V. Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters. Peptides, 2013, 46, 126-135.
Ballinger, A.B.; Williams, G.; Corder, R.; El-Haj, T.; Farthing, M.J. Role of hypothalamic neuropeptide Y and orexigenic peptides in anorexia associated with experimental colitis in the rat. Clin. Sci. (Lond.), 2001, 100, 221-229.
Hasek, L.Y.; Phillips, R.J.; Zhang, G.; Kinzig, K.P.; Kim, C.Y.; Powley, T.L.; Hamaker, B.R. Dietary slowly digestible starch triggers the gut-brain axis in obese rats with accompanied reduced food intake. Mol. Nutr. Food Res., 2018, 62
Meng, F.; Han, Y.; Srisai, D.; Belakhov, V.; Farias, M.; Xu, Y.; Palmiter, R.D.; Baasov, T.; Wu, Q. New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism. Proc. Natl. Acad. Sci. USA, 2016, 113, 3645-3650.
Hohmann, J.G.; Teklemichael, D.N.; Weinshenker, D.; Wynick, D.; Clifton, D.K.; Steiner, R.A. Obesity and endocrine dysfunction in mice with deletions of both neuropeptide Y and galanin. Mol. Cell. Biol., 2004, 24, 2978-2985.
Jin, J.; Xu, G.X.; Yuan, Z.L. Influence of the hypothalamic arcuate nucleus on intraocular pressure and the role of opioid peptides. PLoS One, 2014, 9e82315
Mandelblat-Cerf, Y.; Ramesh, R.N.; Burgess, C.R.; Patella, P.; Yang, Z.; Lowell, B.B.; Andermann, M.L. Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales. eLife, 2015, 4e07122
Lee, B.; Kim, J.; An, T.; Kim, S.; Patel, E.M.; Raber, J.; Lee, S.K.; Lee, S.; Lee, J.W. Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons. Nat. Commun., 2018, 9, 2026.
Reichmann, F.; Holzer, P.; Neuropeptide, Y. A stressful review. Neuropeptides, 2016, 55, 99-109.
Yulyaningsih, E.; Zhang, L.; Herzog, H.; Sainsbury, A. NPY receptors as potential targets for anti-obesity drug development. Br. J. Pharmacol., 2011, 163, 1170-1202.
Zhang, W.; Cline, M.A.; Gilbert, E.R. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism. Nutr. Metab. (Lond.), 2014, 11, 27.
Qi, Y.; Fu, M.; Herzog, H. Y2 receptor signalling in NPY neurons controls bone formation and fasting induced feeding but not spontaneous feeding. Neuropeptides, 2016, 55, 91-97.
Shi, Y.C.; Lin, S.; Wong, I.P.; Baldock, P.A.; Aljanova, A.; Enriquez, R.F.; Castillo, L.; Mitchell, N.F.; Ye, J.M.; Zhang, L.; Macia, L.; Yulyaningsih, E.; Nguyen, A.D.; Riepler, S.J.; Herzog, H.; Sainsbury, A. NPY neuron-specific Y2 receptors regulate adipose tissue and trabecular bone but not cortical bone homeostasis in mice. PLoS One, 2010, 5e11361
Kuo, L.E.; Kitlinska, J.B.; Tilan, J.U.; Li, L.; Baker, S.B.; Johnson, M.D.; Lee, E.W.; Burnett, M.S.; Fricke, S.T.; Kvetnansky, R.; Herzog, H.; Zukowska, Z. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat. Med., 2007, 13, 803-811.
Herzog, H.; Darby, K.; Ball, H.; Hort, Y.; Beck-Sickinger, A.; Shine, J. Overlapping gene structure of the human neuropeptide Y receptor subtypes Y1 and Y5 suggests coordinate transcriptional regulation. Genomics, 1997, 41, 315-319.
Nichol, K.A.; Morey, A.; Couzens, M.H.; Shine, J.; Herzog, H.; Cunningham, A.M. Conservation of expression of neuropeptide Y5 receptor between human and rat hypothalamus and limbic regions suggests an integral role in central neuroendocrine control. J. Neurosci., 1999, 19, 10295-10304.
Shi, Y.C.; Lin, S.; Castillo, L.; Aljanova, A.; Enriquez, R.F.; Nguyen, A.D.; Baldock, P.A.; Zhang, L.; Bijker, M.S.; Macia, L.; Yulyaningsih, E.; Zhang, H.; Lau, J.; Sainsbury, A.; Herzog, H. Peripheral-specific y2 receptor knockdown protects mice from high-fat diet-induced obesity. Obesity (Silver Spring), 2011, 19, 2137-2148.
Liu, S.; Marcelin, G.; Blouet, C.; Jeong, J.H.; Jo, Y.H.; Schwartz, G.J.; Chua, S., Jr A gut-brain axis regulating glucose metabolism mediated by bile acids and competitive fibroblast growth factor actions at the hypothalamus. Mol. Metab., 2018, 8, 37-50.
Laing, B.T.; Li, P.; Schmidt, C.A.; Bunner, W.; Yuan, Y.; Landry, T.; Prete, A.; McClung, J.M.; Huang, H. AgRP/NPY neuron excitability is modulated by metabotropic glutamate receptor 1 during fasting. Front. Cell. Neurosci., 2018, 12, 276.
Yang, K.; Guan, H.; Arany, E.; Hill, D.J.; Cao, X. Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation of adipocyte precursor cells via the Y1 receptor. FASEB J., 2008, 22, 2452-2464.
Loh, K.; Herzog, H.; Shi, Y.C. Regulation of energy homeostasis by the NPY system. Trends Endocrinol. Metab., 2015, 26, 125-135.
Steinert, R.E.; Feinle-Bisset, C.; Asarian, L.; Horowitz, M.; Beglinger, C.; Geary, N. Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol. Rev., 2017, 97, 411-463.
Chandarana, K.; Drew, M.E.; Emmanuel, J.; Karra, E.; Gelegen, C.; Chan, P.; Cron, N.J.; Batterham, R.L. Subject standardization, acclimatization, and sample processing affect gut hormone levels and appetite in humans. Gastroenterology, 2009, 136, 2115-2126.
Hill, B.R.; De Souza, M.J.; Williams, N.I. Characterization of the diurnal rhythm of peptide YY and its association with energy balance parameters in normal-weight premenopausal women. Am. J. Physiol. Endocrinol. Metab., 2011, 301, E409-E415.
Holzer, P.; Reichmann, F.; Farzi, A. Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides, 2012, 46, 261-274.
Batterham, R.L.; Heffron, H.; Kapoor, S.; Chivers, J.E.; Chandarana, K.; Herzog, H.; Le Roux, C.W.; Thomas, E.L.; Bell, J.D.; Withers, D.J. Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab., 2006, 4, 223-233.
Sedlackova, D.; Kopeckova, J.; Papezova, H.; Hainer, V.; Kvasnickova, H.; Hill, M.; Nedvidkova, J. Comparison of a high-carbohydrate and high-protein breakfast effect on plasma ghrelin, obestatin, NPY and PYY levels in women with anorexia and bulimia nervosa. Nutr. Metab. (Lond.), 2012, 9, 52.
Ballantyne, G.H. Peptide YY(1-36) and peptide YY(3-36): Part I. Distribution, release and actions. Obes. Surg., 2006, 16, 651-658.
Nadkarni, P.P.; Costanzo, R.M.; Sakagami, M. Pulmonary delivery of peptide YY for food intake suppression and reduced body weight gain in rats. Diabetes Obes. Metab., 2011, 13, 408-417.
Sloth, B.; Davidsen, L.; Holst, J.J.; Flint, A.; Astrup, A. Effect of subcutaneous injections of PYY1-36 and PYY3-36 on appetite, ad libitum energy intake, and plasma free fatty acid concentration in obese males. Am. J. Physiol. Endocrinol. Metab., 2007, 293, E604-E609.
Batterham, R.L.; Cowley, M.A.; Small, C.J.; Herzog, H.; Cohen, M.A.; Dakin, C.L.; Wren, A.M.; Brynes, A.E.; Low, M.J.; Ghatei, M.A.; Cone, R.D.; Bloom, S.R. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature, 2002, 418, 650-654.
Batterham, R.L. ffytche, D.H.; Rosenthal, J.M.; Zelaya, F.O.; Barker, G.J.; Withers, D.J.; Williams, S.C. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Nature, 2007, 450, 106-109.
Alhadeff, A.L.; Golub, D.; Hayes, M.R.; Grill, H.J. Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor. Am. J. Physiol. Endocrinol. Metab., 2015, 309, E759-E766.
Teubner, B.J.; Bartness, T.J. PYY(3-36) into the arcuate nucleus inhibits food deprivation-induced increases in food hoarding and intake. Peptides, 2013, 47, 20-28.
Suzuki, Y.; Nakahara, K.; Maruyama, K.; Okame, R.; Ensho, T.; Inoue, Y.; Murakami, N. Changes in mRNA expression of arcuate nucleus appetite-regulating peptides during lactation in rats. J. Mol. Endocrinol., 2014, 52, 97-109.
Minor, R.K.; Chang, J.W.; de Cabo, R. Hungry for life: How the arcuate nucleus and neuropeptide Y may play a critical role in mediating the benefits of calorie restriction. Mol. Cell. Endocrinol., 2009, 299, 79-88.
Abbott, C.R.; Small, C.J.; Kennedy, A.R.; Neary, N.M.; Sajedi, A.; Ghatei, M.A.; Bloom, S.R. Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3-36) on food intake. Brain Res., 2005, 1043, 139-144.
Zhang, L.; Nguyen, A.D.; Lee, I.C.; Yulyaningsih, E.; Riepler, S.J.; Stehrer, B.; Enriquez, R.F.; Lin, S.; Shi, Y.C.; Baldock, P.A.; Sainsbury, A.; Herzog, H. NPY modulates PYY function in the regulation of energy balance and glucose homeostasis. Diabetes Obes. Metab., 2012, 14, 727-736.
He, T.; He, L.; Gao, E.; Hu, J.; Zang, J.; Wang, C.; Zhao, J.; Ma, X. Fat deposition deficiency is critical for the high mortality of pre-weanling newborn piglets. J. Anim. Sci. Biotechnol., 2018, 9, 66.
Huang, X.F.; Yu, Y.; Beck, E.J.; South, T.; Li, Y.; Batterham, M.J.; Tapsell, L.C.; Chen, J. Diet high in oat β-glucan activates the gut-hypothalamic (PYY3-36-NPY) axis and increases satiety in diet-induced obesity in mice. Mol. Nutr. Food Res., 2011, 55, 1118-1121.
Konturek, S.J.; Konturek, J.W.; Pawlik, T.; Brzozowski, T. Brain‐gut axis and its role in the control of food intake. J. Physiol. Pharmacol., 2004, 55, 137-154.
Schéle, E.; Grahnemo, L.; Anesten, F.; Halleń, A.; Backhed, F.; Jansson, J.O. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system. Endocrinology, 2013, 154, 3643-3651.
Rao, S.; Schieber, A.M.P.; O’Connor, C.P.; Leblanc, M.; Michel, D.; Ayres, J.S. Pathogen-mediated inhibition of anorexia promotes host survival and transmission. Cell, 2017, 168, 503-516.
Husebye, E.; Hellström, P.M.; Sundler, F.; Chen, J.; Midtvedt, T. Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 280, G368-G380.
El Karim, I.A.; Linden, G.J.; Orr, D.F.; Lundy, F.T. Antimicrobial activity of neuropeptides against a range of micro-organisms from skin, oral, respiratory and gastrointestinal tract sites. J. Neuroimmunol., 2008, 200, 11-16.
Liu, R.; Zhang, C.; Shi, Y.; Zhang, F.; Li, L.; Wang, X.; Ling, Y.; Fu, H.; Dong, W.; Shen, J.; Reeves, A.; Greenberg, A.S.; Zhao, L.; Peng, Y.; Ding, X. Dysbiosis of gut microbiota associated with clinical parameters in polycystic ovary syndrome. Front. Microbiol., 2017, 8, 324.
Chambers, E.S.; Viardot, A.; Psichas, A.; Morrison, D.J.; Murphy, K.G.; Zac-Varghese, S.E.; MacDougall, K.; Preston, T.; Tedford, C.; Finlayson, G.S.; Blundell, J.E.; Bell, J.D.; Thomas, E.L.; Mt-Isa, S.; Ashby, D.; Gibson, G.R.; Kolida, S.; Dhillo, W.S.; Bloom, S.R.; Morley, W.; Clegg, S.; Frost, G. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut, 2015, 64, 1744-1754.
Samuel, B.S.; Shaito, A.; Motoike, T.; Rey, F.E.; Backhed, F.; Manchester, J.K.; Hammer, R.E.; Williams, S.C.; Crowley, J.; Yanagisawa, M.; Gordon, J.I. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. USA, 2008, 105, 16767-16772.
Larraufie, P.; Doré, J.; Lapaque, N.; Blottière, H.M. TLR ligands and butyrate increase Pyy expression through two distinct but inter-regulated pathways. Cell. Microbiol., 2017, 19e12648
Huang, C.; Song, P.; Fan, P.; Hou, C.; Thacker, P.A.; Ma, X. Dietary sodium butyrate decreased postweaning diarrhea by modulating intestinal permeability and changing the bacterial community in weaned piglets. J. Nutr., 2015, 145, 2774-2780.
Goodlad, R.A.; Ratcliffe, B.; Fordham, J.P.; Ghatei, M.A.; Domin, J.; Bloom, S.R.; Wright, N.A. Plasma enteroglucagon, gastrin and peptide YY in conventional and germ-free rats refed with a fibre-free or fibre-supplemented diet. Q. J. Exp. Physiol., 1989, 74, 437-442.
Hong, K.B.; Kim, J.H.; Kwon, H.K.; Han, S.H.; Park, Y.; Suh, H.J. Evaluation of prebiotic effects of high-purity galactooligosaccharides in vitro and in vivo. Food Technol. Biotechnol., 2016, 54, 156-163.
van der Beek, C.M.; Canfora, E.E.; Kip, A.M.; Gorissen, S.H.M.; Olde Damink, S.W.M.; van Eijk, H.M.; Holst, J.J.; Blaak, E.E.; Dejong, C.H.C.; Lenaerts, K. The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men. Metabolism, 2018, 87, 25-35.
Rahat-Rozenbloom, S.; Fernandes, J.; Cheng, J.; Wolever, T.M.S. Acute increases in serum colonic short-chain fatty acids elicited by inulin do not increase GLP-1 or PYY responses but may reduce ghrelin in lean and overweight humans. Eur. J. Clin. Nutr., 2017, 71, 953-958.
Nilsson, A.; Johansson-Boll, E.; Sandberg, J.; Björck, I. Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics: A randomized controlled study in healthy subjects. Clin. Nutr. ESPEN, 2016, 15, 49-56.
Yang, Z.; Han, S.; Keller, M.; Kaiser, A.; Bender, B.J.; Bosse, M.; Burkert, K.; Kögler, L.M.; Wifling, D.; Bernhardt, G.; Plank, N.; Littmann, T.; Schmidt, P.; Yi, C.; Li, B.; Ye, S.; Zhang, R.; Xu, B.; Larhammar, D.; Stevens, R.C.; Huster, D.; Meiler, J.; Zhao, Q. Beck-Sickinger, A.G.; Buschauer, A.; Wu, B. Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor. Nature, 2018, 556, 520-524.

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Article Details

Year: 2019
Page: [750 - 758]
Pages: 9
DOI: 10.2174/1389203720666190125105401
Price: $58

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