Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome
Open accessAbstract
Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient-gut microbiota interaction and subsequent parasympathetic activation as possible therapeutic targets for obesity.
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Acetate is present in cerebrospinal fluid, and gut microbial-derived acetate reaches the brain and triggers PNS signaling.
“Specifically, acetate has been reported to be present in the cerebrospinal fluid, and gut microbial-derived acetate has been shown to reach the brain and trigger PNS signaling (Nagashima et al., 2010;Perry et al., 2016).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Perry et al., 2016
The gut microbiome and its metabolites modulate ghrelin secretion and CNS functions.
“The gut microbiome, along with its metabolites, has been reported to modulate ghrelin secretion and CNS functions.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [552]
Free short-chain fatty acid levels are virtually undetectable in plasma recovered from germ-free animals.
“The idea that circulating SCFAs are produced in large part by gut commensals is supported by studies showing that free SCFA levels are virtually undetectable in plasma recovered from germ-free animals51.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [51]
Germ-free mice have lower levels of plasma ghrelin under basal conditions than conventional mice.
“Indeed, germ-free mice have lower levels of plasma ghrelin under basal conditions than conventional mice [128,129].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [129]
Increased acetate production by gut bacteria promotes insulin secretion, hyperphagia, and obesity.
“increased acetate production by gut bacteria has been found recently to promote insulin secretion, hyperphagia, and obesity [22]”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [22]
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Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444 · see citing works
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100 · see citing works
Murphy, E. F., Cotter, P. D., Healy, S., Marques, T. M., O’Sullivan, Ó., Fouhy, F., Clarke, S. F., O’Toole, P. W., Quigley, E. M. M., Stanton, C., et al. (2010) · Gut · doi:10.1136/gut.2010.215665 · Cited by 942 · see citing works
Autonomic regulation of islet hormone secretion – Implications for health and disease
Bo, A.-R. (2000) · Diabetologia · doi:10.1007/s001250051322 · Cited by 843 · see citing works
Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans
Fernandes, J., Su, W., Rahat-Rozenbloom, S., Wolever, T. M. S., & Comelli, E. M. (2014) · Nutrition & Diabetes · doi:10.1038/nutd.2014.23 · Cited by 628 · see citing works
The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion
MacDonald, P. E., El-kholy, W., Riedel, M. J., Salapatek, A. M. F., Light, P. E., & Wheeler, M. B. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s434 · Cited by 590 · see citing works
Minireview: The Glucagon-Like Peptides
Drucker, D. J. (2001) · Endocrinology · doi:10.1210/endo.142.2.7983 · Cited by 421 · see citing works
Microbial Modulation of Energy Availability in the Colon Regulates Intestinal Transit
Wichmann, A., Allahyar, A., Greiner, T. U., Plovier, H., Östergren‐Lundén, G., Larsson, T. P., Drucker, D. J., Delzenne, N. M., Cani, P. D., & Bäckhed, F. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.09.012 · Cited by 382 · see citing works
Ahrén, B., & Holst, J. J. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1030 · Cited by 292 · see citing works
Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans
Rahat-Rozenbloom, S., Fernandes, J., Gloor, G. B., & Wolever, T. M. S. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.46 · Cited by 290 · see citing works
Effect of Vagotomy and Vagal Stimulation on Insulin Secretion
Frohman, L. A., Ezdinli, E. Z., & Javid, R. (1967) · Diabetes · doi:10.2337/diab.16.7.443 · Cited by 249 · see citing works
Murugesan, S., Ulloa-Martínez, M., Martínez‐Rojano, H., Galván-Rodríguez, F. M., Miranda-Brito, C., Romano, M. C., Piña-Escobedo, A., Pizano-Zárate, M. L., Hoyo‐Vadillo, C., & Garcı́a-Mena, J. (2015) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-015-2355-4 · Cited by 170 · see citing works
Direct enhancement of insulin secretion by vagal stimulation of the isolated pancreas
Bergman, R. N., & Miller, R. (1973) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1973.225.2.481 · Cited by 113 · see citing works
Aguirre, M., Jonkers, D. M. A. E., Troost, F. J., Roeselers, G., & Venema, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113864 · Cited by 108 · see citing works
D’Alessio, D. A., Kieffer, T. J., Taborsky, G. J., & Havel, P. J. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7367 · Cited by 96 · see citing works
Ionescu, E., Rohner‐Jeanrenaud, F., Berthoud, H., & Jeanrenaud, B. (1983) · Endocrinology · doi:10.1210/endo-112-3-904 · Cited by 94 · see citing works
The Hepatic Vagus Nerve and the Neural Regulation of Insulin Secretion*
Lee, K. C., & Miller, R. E. (1985) · Endocrinology · doi:10.1210/endo-117-1-307 · Cited by 93 · see citing works
Distinct gut microbiota of healthy children from two different geographic regions of Thailand
La-ongkham, O., Nakphaichit, M., Leelavatcharamas, V., Keawsompong, S., & Nitisinprasert, S. (2015) · Archives of Microbiology · doi:10.1007/s00203-015-1089-0 · Cited by 64 · see citing works
Ronnebaum, S. M., Joseph, J. W., Ilkayeva, O., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800119200 · Cited by 54 · see citing works
Li, M., Gu, D., Xu, N., Lei, F., Du, L., Zhang, Y., & Xie, W. (2014) · Beneficial Microbes · doi:10.3920/bm2013.0071 · Cited by 33 · see citing works
Sakaguchi, T., & Yamaguchi, K. (1979) · Brain Research · doi:10.1016/0006-8993(79)90028-3 · Cited by 32 · see citing works
Shen, W., Liu, K., Tian, C., Lu, Y., Li, X., Ren, J., Packer, L., Head, E., Sharman, E. H., & Liu, J. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21701 · Cited by 31 · see citing works
Shepherd, M. L., Ponder, M. A., Burk, A. O., Milton, S. C., & Swecker, W. S. (2014) · Journal of Nutritional Science · doi:10.1017/jns.2014.8 · Cited by 19 · see citing works
Yamazaki, H., Philbrick, W. M., Zawalich, K. C., & Zawalich, W. S. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00149.2005 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Gut microbiota in human metabolic health and disease
Fan, Y., & Pedersen, O. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0433-9 · Cited by 4,724 · see citing works
The role of short-chain fatty acids in microbiota–gut–brain communication
Dalile, B., Van Oudenhove, L., Vervliet, B., & Verbeke, K. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0157-3 · Cited by 3,357 · see citing works
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028 · see citing works
Self-citationYou are what you eat: Diet, health and the gut microbiota
Zmora, N., Suez, J., & Elinav, E. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0061-2 · Cited by 1,792 · see citing works
Dietary fiber and prebiotics and the gastrointestinal microbiota
Holscher, H. D. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1290756 · Cited by 1,808 · see citing works
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
The intestinal microbiota fuelling metabolic inflammation
Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0198-4 · Cited by 1,089 · see citing works
Short chain fatty acids in human gut and metabolic health
Blaak, E. E., Canfora, E. E., Theis, S., Frost, G., Groen, A. K., Mithieux, G., Nauta, A., Scott, K., Stahl, B., van Harsselaar, J., et al. (2020) · Beneficial Microbes · doi:10.3920/bm2020.0057 · Cited by 1,103 · see citing works
Psychobiotics and the manipulation of bacteria–gut–brain signals
Sarkar, A., Lehto, S. M., Harty, S., Dinan, T. G., Cryan, J. F., & Burnet, P. W. J. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.09.002 · Cited by 1,068 · see citing works
Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
van de Wouw, M., Boehme, M., Lyte, J. M., Wiley, N., Strain, C., O'Sullivan, O., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2018) · The Journal of Physiology · doi:10.1113/jp276431 · Cited by 789 · see citing works
Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health
Chambers, E. S., Preston, T., Frost, G., & Morrison, D. J. (2018) · Current Nutrition Reports · doi:10.1007/s13668-018-0248-8 · Cited by 691 · see citing works
Mariño, E., Richards, J. L., McLeod, K. H., Stanley, D., Yap, Y. A., Knight, J., McKenzie, C., Kranich, J., Oliveira, A. C., Rossello, F. J., et al. (2017) · Nature Immunology · doi:10.1038/ni.3713 · Cited by 686 · see citing works
Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit
Li, Z., Yi, C.-X., Katiraei, S., Kooijman, S., Zhou, E., Chung, C. K., Gao, Y., van den Heuvel, J. K., Meijer, O. C., Berbée, J. F. P., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-314050 · Cited by 674 · see citing works
Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues
Krautkramer, K. A., Kreznar, J. H., Romano, K. A., Vivas, E. I., Barrett-Wilt, G. A., Rabaglia, M. E., Keller, M. P., Attie, A. D., Rey, F. E., & Denu, J. M. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.10.025 · Cited by 607 · see citing works
Comprehensive quantification of fuel use by the failing and nonfailing human heart
Murashige, D., Jang, C., Neinast, M., Edwards, J. J., Cowan, A., Hyman, M. C., Rabinowitz, J. D., Frankel, D. S., & Arany, Z. (2020) · Science · doi:10.1126/science.abc8861 · Cited by 580 · see citing works
Anxiety, depression, and the microbiome: A role for gut peptides
Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0585-0 · Cited by 573 · see citing works
Anticancer effects of the microbiome and its products
Zitvogel, L., Daillère, R., Roberti, M. P., Routy, B., & Kroemer, G. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.44 · Cited by 538 · see citing works
Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer
Singh, V., Yeoh, B. S., Chassaing, B., Xiao, X., Saha, P., Aguilera Olvera, R., Lapek, J. D., Zhang, L., Wang, W.-B., Hao, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.004 · Cited by 532 · see citing works
Gut microbiome and liver diseases
Tilg, H., Cani, P. D., & Mayer, E. A. (2016) · Gut · doi:10.1136/gutjnl-2016-312729 · Cited by 525 · see citing works
Erny, D., Dokalis, N., Mezö, C., Castoldi, A., Mossad, O., Staszewski, O., Frosch, M., Villa, M., Fuchs, V., Mayer, A., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.10.010 · Cited by 478 · see citing works
Microbiota-gut-brain axis: Modulator of host metabolism and appetite
van de Wouw, M., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017) · The Journal of Nutrition · doi:10.3945/jn.116.240481 · Cited by 461 · see citing works
Obesity pandemic: causes, consequences, and solutions—but do we have the will?
Meldrum, D. R., Morris, M. A., & Gambone, J. C. (2017) · Fertility and Sterility · doi:10.1016/j.fertnstert.2017.02.104 · Cited by 457 · see citing works
Natarajan, N., Hori, D., Flavahan, S., Steppan, J., Flavahan, N. A., Berkowitz, D. E., & Pluznick, J. L. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00089.2016 · Cited by 441 · see citing works
The progress of gut microbiome research related to brain disorders
Zhu, S., Jiang, Y., Xu, K., Cui, M., Ye, W., Zhao, G., Jin, L., & Chen, X. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1705-z · Cited by 419 · see citing works
Ticinesi, A., Lauretani, F., Milani, C., Nouvenne, A., Tana, C., Del Rio, D., Maggio, M., Ventura, M., & Meschi, T. (2017) · Nutrients · doi:10.3390/nu9121303 · Cited by 401 · see citing works
ATP-citrate lyase controls a glucose-to-acetate metabolic switch
Zhao, S., Torres, A., Henry, R. A., Trefely, S., Wallace, M., Lee, J. V., Carrer, A., Sengupta, A., Campbell, S. L., Kuo, Y.-M., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.069 · Cited by 394 · see citing works
Brain–gut–microbiota axis — mood, metabolism and behaviour
Dinan, T. G., & Cryan, J. F. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.200 · Cited by 361 · see citing works
Gut Microbiome Dysbiosis and Immunometabolism: New Frontiers for Treatment of Metabolic Diseases
Belizário, J. E., Faintuch, J., & Garay-Malpartida, M. (2018) · Mediators of Inflammation · doi:10.1155/2018/2037838 · Cited by 341 · see citing works
Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS
Liu, L., Huh, J. R., & Shah, K. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.103908 · Cited by 344 · see citing works
Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet
Bisanz, J. E., Upadhyay, V., Turnbaugh, J. A., Ly, K., & Turnbaugh, P. J. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.06.013 · Cited by 333 · see citing works
Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity
Chun, E., Lavoie, S., Fonseca-Pereira, D., Bae, S., Michaud, M., Hoveyda, H. R., Fraser, G. L., Gallini Comeau, C. A., Glickman, J. N., Fuller, M. H., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.09.014 · Cited by 336 · see citing works
Human tissues in a dish: The research and ethical implications of organoid technology
Bredenoord, A. L., Clevers, H., & Knoblich, J. A. (2017) · Science · doi:10.1126/science.aaf9414 · Cited by 334 · see citing works
Benedict, C., Vogel, H., Jonas, W., Woting, A., Blaut, M., Schürmann, A., & Cedernaes, J. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.10.003 · Cited by 324 · see citing works
Wang, Y., Tong, Q., Ma, S.-R., Zhao, Z.-X., Pan, L.-B., Cong, L., Han, P., Peng, R., Yu, H., Lin, Y., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00456-5 · Cited by 319 · see citing works
Microbial Short-Chain Fatty Acids and Blood Pressure Regulation
Pluznick, J. L. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0722-5 · Cited by 301 · see citing works
From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators
Han, H., Yi, B., Zhong, R., Wang, M., Zhang, S., Ma, J., Yin, Y., Yin, J., Chen, L., & Zhang, H. (2021) · Microbiome · doi:10.1186/s40168-021-01093-y · Cited by 292 · see citing works
Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health
Parkar, S. G., Kalsbeek, A., & Cheeseman, J. F. (2019) · Microorganisms · doi:10.3390/microorganisms7020041 · Cited by 285 · see citing works
The Mouse Microbiome Is Required for Sex-Specific Diurnal Rhythms of Gene Expression and Metabolism
Weger, B. D., Gobet, C., Yeung, J., Martin, E., Jimenez, S., Betrisey, B., Foata, F., Berger, B., Balvay, A., Foussier, A., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.09.023 · Cited by 269 · see citing works
Bauer, P. V., Duca, F. A., Waise, T. M. Z., Rasmussen, B. A., Abraham, M. A., Dranse, H. J., Puri, A., O’Brien, C. A., & Lam, T. K. T. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.019 · Cited by 265 · see citing works
Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact, and Mechanisms
Corbin, K. D., Driscoll, K. A., Pratley, R. E., Smith, S. R., Maahs, D. M., Mayer-Davis, E. J., & Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) (2018) · Endocrine Reviews · doi:10.1210/er.2017-00191 · Cited by 262 · see citing works
Inter-organ crosstalk during development and progression of type 2 diabetes mellitus
Xourafa, G., Korbmacher, M., & Roden, M. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00898-1 · Cited by 274 · see citing works
Gut microbiota in the pathogenesis and therapeutic approaches of diabetes
Crudele, L., Gadaleta, R. M., Cariello, M., & Moschetta, A. (2023) · eBioMedicine · doi:10.1016/j.ebiom.2023.104821 · Cited by 251 · see citing works
Diet, genetics, and the gut microbiome drive dynamic changes in plasma metabolites
Fujisaka, S., Avila-Pacheco, J., Soto, M., Kostic, A., Dreyfuss, J. M., Pan, H., Ussar, S., Altindis, E., Li, N., Bry, L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.060 · Cited by 231 · see citing works
“…butyrate, and propionate not only serve as important energy sources for the intestinal epithelium and the liver but can also can modify insulin secretion, immune system function, appetite, and adipose function (Bouter et al., 2017; Canfora et al., 2015; Holmes et al., 2012; Perry et al., 2016).”
BackgroundSpiljar, M., Merkler, D., & Trajkovski, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01353 · Cited by 219 · see citing works
Korcz, E., Kerényi, Z., & Varga, L. (2018) · Food & Function · doi:10.1039/c8fo00118a · Cited by 222 · see citing works
Microbiome potentiates endurance exercise through intestinal acetate production
Okamoto, T., Morino, K., Ugi, S., Nakagawa, F., Lemecha, M., Ida, S., Ohashi, N., Sato, D., Fujita, Y., & Maegawa, H. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00510.2018 · Cited by 210 · see citing works
Deciphering the Chemical Lexicon of Host–Gut Microbiota Interactions
Nicolas, G. R., & Chang, P. V. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.04.006 · Cited by 195 · see citing works
Kaczmarek, J. L., Musaad, S. M., & Holscher, H. D. (2017) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.156380 · Cited by 200 · see citing works
Host genotype and gut microbiome modulate insulin secretion and diet-induced metabolic phenotypes
Kreznar, J. H., Keller, M. P., Traeger, L. L., Rabaglia, M. E., Schueler, K. L., Stapleton, D. S., Zhao, W., Vivas, E. I., Yandell, B. S., Broman, A. T., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.01.062 · Cited by 177 · see citing works
Raw meat based diet influences faecal microbiome and end products of fermentation in healthy dogs
Sandri, M., Dal Monego, S., Conte, G., Sgorlon, S., & Stefanon, B. (2016) · BMC Veterinary Research · doi:10.1186/s12917-017-0981-z · Cited by 185 · see citing works
Gut microbiota–derived short-chain fatty acids and kidney diseases
Li, L., Ma, L., & Fu, P. (2017) · Drug Design, Development and Therapy · doi:10.2147/dddt.s150825 · Cited by 164 · see citing works
Feeding the microbiota: Transducer of nutrient signals for the host
Shanahan, F., van Sinderen, D., O’Toole, P. W., & Stanton, C. (2017) · Gut · doi:10.1136/gutjnl-2017-313872 · Cited by 157 · see citing works
Short-chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling
Torres‐Fuentes, C., Golubeva, A. V., Zhdanov, A. V., Wallace, S., Arboleya, S., Papkovsky, D. B., Aidy, S. E., Ross, P., Roy, B. L., Stanton, C., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901433r · Cited by 154 · see citing works
Uchimura, Y., Fuhrer, T., Li, H., Lawson, M. A., Zimmermann, M., Yilmaz, B., Zindel, J., Ronchi, F., Sorribas, M., Hapfelmeier, S., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.08.004 · Cited by 153 · see citing works
Autophagy Differentially Regulates Insulin Production and Insulin Sensitivity
Yamamoto, S., Kuramoto, K., Wang, N., Situ, X., Priyadarshini, M., Zhang, W., Cordoba-Chacon, J., Layden, B. T., & He, C. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.032 · Cited by 144 · see citing works
Gut hormones in microbiota-gut-brain cross-talk
Sun, L.-J., Li, J.-N., & Nie, Y.-Z. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000706 · Cited by 145 · see citing works
Metformin and gut microbiota: their interactions and their impact on diabetes
Vallianou, N. G., Stratigou, T., & Tsagarakis, S. (2019) · Hormones · doi:10.1007/s42000-019-00093-w · Cited by 138 · see citing works
The role of the microbiome in the neurobiology of social behaviour
Sarkar, A., Harty, S., Johnson, K. V. ‐., Moeller, A. H., Carmody, R. N., Lehto, S. M., Erdman, S. E., Dunbar, R. I. M., & Burnet, P. W. J. (2020) · Biological Reviews · doi:10.1111/brv.12603 · Cited by 135 · see citing works
The gut microbiome in psoriasis and psoriatic arthritis
Myers, B., Brownstone, N., Reddy, V., Chan, S., Thibodeaux, Q., Truong, A., Bhutani, T., Chang, H.-W., & Liao, W. (2019) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2020.101494 · Cited by 127 · see citing works
Kao, A. C.-C., Spitzer, S., Anthony, D. C., Lennox, B., & Burnet, P. W. J. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0116-8 · Cited by 128 · see citing works
KUWAHARA, A., MATSUDA, K., KUWAHARA, Y., ASANO, S., INUI, T., & MARUNAKA, Y. (2020) · Biomedical Research · doi:10.2220/biomedres.41.199 · Cited by 112 · see citing works
Links between Dietary Protein Sources, the Gut Microbiota, and Obesity
Madsen, L., Myrmel, L. S., Fjære, E., Liaset, B., & Kristiansen, K. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.01047 · Cited by 110 · see citing works
Nash, M. J., Frank, D. N., & Friedman, J. E. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00349 · Cited by 101 · see citing works
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Pollak, M. (2017) · Diabetologia · doi:10.1007/s00125-017-4352-x · Cited by 98 · see citing works
Janssen, A. W. F., Katiraei, S., Bartosinska, B., Eberhard, D., Willems van Dijk, K., & Kersten, S. (2018) · Diabetologia · doi:10.1007/s00125-018-4583-5 · Cited by 96 · see citing works
Song, L., Sun, Q., Zheng, H., Zhang, Y., Wang, Y., Liu, S., & Duan, L. (2022) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202200164 · Cited by 91 · see citing works
Tanca, A., Abbondio, M., Palomba, A., Fraumene, C., Marongiu, F., Serra, M., Pagnozzi, D., Laconi, E., & Uzzau, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-33100-y · Cited by 79 · see citing works
Zhang, Q., Pan, Y., Zeng, B., Zheng, X., Wang, H., Shen, X., Li, H., Jiang, Q., Zhao, J., Meng, Z.-X., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0190-3 · Cited by 73 · see citing works
Gut Microbiome and Modulation of <scp>CNS</scp> Function
Osadchiy, V., Martin, C. R., & Mayer, E. A. (2019) · Comprehensive Physiology · doi:10.1002/cphy.c180031 · Cited by 53 · see citing works
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Al-Rubaye, H., Perfetti, G., & Kaski, J.-C. (2019) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2018.06.005 · Cited by 43 · see citing works
Dagbasi, A., Lett, A. M., Murphy, K., & Frost, G. (2020) · Proceedings of the Nutrition Society · doi:10.1017/s0029665120006941 · Cited by 44 · see citing works
Ren, Z., Xu, Y., Li, T., Sun, W., Tang, Z., Wang, Y., Zhou, K., Li, J., Ding, Q., Liang, K., et al. (2022) · Animal Nutrition · doi:10.1016/j.aninu.2022.06.009 · Cited by 44 · see citing works
Kao, A. C.-C., Chan, K. W., Anthony, D. C., Lennox, B. R., & Burnet, P. W. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.02.014 · Cited by 32 · see citing works
Gut Microbiota Restores Central Neuropeptide Deficits in Germ-Free Mice
Hamamah, S., & Covasa, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911756 · Cited by 25 · see citing works
Wu, W., Chen, Z., Han, J., Qian, L., Wang, W., Lei, J., & Wang, H. (2023) · Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity · doi:10.1007/s40519-023-01593-w · Cited by 18 · see citing works
Chen, H., Cao, T., Zhang, B., & Cai, H. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1097284 · Cited by 18 · see citing works
Acylation, a Conductor of Ghrelin Function in Brain Health and Disease
Thomas, A. S., Sassi, M., Angelini, R., Morgan, A. H., & Davies, J. S. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.831641 · Cited by 17 · see citing works
- Authors
- 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.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- University of Copenhagen (DK)
- Corresponding author
- Shulman, Gerald I.
- ORCID
- Venue
- Nature
- Published
- 2016-06-08
- Volume
- 534
- Issue
- 7606
- Pages
- 213-217
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4922538
- OpenAlex
- W2417777372
- Cited by
- 1,299
- References
- 24
- Citations by year
- 2026: 83 · 2025: 108 · 2024: 142 · 2023: 142 · 2022: 141 · 2021: 146 · 2020: 131 · 2019: 140 · 2018: 128 · 2017: 99 · 2016: 39
- FWCI
- 70.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (UL1TR001863)
- National Institute on Aging (R01AG023686)
- National Institute of General Medical Sciences (DP2GM105456, R01GM103574)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK101019, R01DK040936, U24DK059635, K01DK089121, R01DK092606, P30DK034989, P30DK045735)
- National Center for Chronic Disease Prevention and Health Promotion (DP2 GM-105456)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- acetate, gut microbiota, beta-cell function, parasympathetic nervous system, metabolic syndrome, obesity, insulin resistance, glucose-stimulated insulin secretion, ghrelin, hyperphagia, high-fat diet, short-chain fatty acids
- MeSH terms
- Gastrointestinal Microbiome, Insulin Secretion, Acetates, Animals, Brain, Glucose, Hyperphagia, Insulin, Obesity, Parasympathetic Nervous System, Metabolic Syndrome, Insulin-Secreting Cells, Rats, Ghrelin, Diet, High-Fat
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