Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1

Anjani, 2015, Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity, J. Hepatol., 62, 905, 10.1016/j.jhep.2014.11.002

Aronov, 2011, Colonic contribution to uremic solutes, J. Am. Soc. Nephrol., 22, 1769, 10.1681/ASN.2010121220

Ashwell, 2006, The many paths to p38 mitogen-activated protein kinase activation in the immune system, Nat. Rev. Immunol., 6, 532, 10.1038/nri1865

Beardmore, 2005, Generation and characterization of p38beta (MAPK11) gene-targeted mice, Mol. Cell. Biol., 25, 10454, 10.1128/MCB.25.23.10454-10464.2005

Beenstock, 2014, The p38β mitogen-activated protein kinase possesses an intrinsic autophosphorylation activity, generated by a short region composed of the α-G helix and MAPK insert, J. Biol. Chem., 289, 23546, 10.1074/jbc.M114.578237

Bender, 2012, Regulation of the histidine utilization (hut) system in bacteria, Microbiol. Mol. Biol. Rev., 76, 565, 10.1128/MMBR.00014-12

Benjamini, 1995, Controlling the false discovery rate - a practical and powerful approach to multiple testing, J. R. Stat. Soc. Series B Stat. Methodol., 57, 289, 10.1111/j.2517-6161.1995.tb02031.x

Blagosklonny, 2013, TOR-centric view on insulin resistance and diabetic complications: perspective for endocrinologists and gerontologists, Cell Death Dis., 4, e964, 10.1038/cddis.2013.506

Bogachev, 2012, Urocanate reductase: identification of a novel anaerobic respiratory pathway in Shewanella oneidensis MR-1, Mol. Microbiol., 86, 1452, 10.1111/mmi.12067

Camacho, 2009, BLAST+: architecture and applications, BMC Bioinformatics, 10, 421, 10.1186/1471-2105-10-421

Chen, 2009, Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro, Nutrition, 25, 340, 10.1016/j.nut.2008.08.012

Copp, 2009, TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2, Cancer Res., 69, 1821, 10.1158/0008-5472.CAN-08-3014

Cotillard, 2013, Dietary intervention impact on gut microbial gene richness, Nature, 500, 585, 10.1038/nature12480

Cuenda, 2007, p38 MAP-kinases pathway regulation, function and role in human diseases, Biochim. Biophys. Acta, 1773, 1358, 10.1016/j.bbamcr.2007.03.010

Dodd, 2017, A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites, Nature, 551, 648, 10.1038/nature24661

Duran, 2011, p62 is a key regulator of nutrient sensing in the mTORC1 pathway, Mol. Cell, 44, 134, 10.1016/j.molcel.2011.06.038

Esposito, 2001, Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells, Endocrinology, 142, 2833, 10.1210/endo.142.7.8283

Finn, 2011, HMMER web server: interactive sequence similarity searching, Nucleic Acids Res., 39, 10.1093/nar/gkr367

Finn, 2016, The Pfam protein families database: towards a more sustainable future, Nucleic Acids Res., 44, D279, 10.1093/nar/gkv1344

Gaba, 2016, Development of drugs based on imidazole and benzimidazole bioactive heterocycles: recent advances and future directions, Med. Chem. Res., 25, 173, 10.1007/s00044-015-1495-5

Ge, 2002, MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha, Science, 295, 1291, 10.1126/science.1067289

González-Terán, 2016, p38γ and p38δ reprogram liver metabolism by modulating neutrophil infiltration, EMBO J., 35, 536, 10.15252/embj.201591857

Harrington, 2004, The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins, J. Cell Biol., 166, 213, 10.1083/jcb.200403069

Kanehisa, 2000, KEGG: kyoto encyclopedia of genes and genomes, Nucleic Acids Res., 28, 27, 10.1093/nar/28.1.27

Karlsson, 2013, Gut metagenome in European women with normal, impaired and diabetic glucose control, Nature, 498, 99, 10.1038/nature12198

Karlsson, 2014, Metagenomic data utilization and analysis (MEDUSA) and construction of a global gut microbial gene catalogue, PLoS Comput. Biol., 10, e1003706, 10.1371/journal.pcbi.1003706

Kikuchi, 2017, Uremic toxin-producing gut microbiota in rats with chronic kidney disease, Nephron, 135, 51, 10.1159/000450619

Kim, 2005, p38 MAPK autophosphorylation drives macrophage IL-12 production during intracellular infection, J. Immunol., 174, 4178, 10.4049/jimmunol.174.7.4178

Kim, 2012, SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling, Mol. Cell, 46, 833, 10.1016/j.molcel.2012.04.007

Koeth, 2013, Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat. Med., 19, 576, 10.1038/nm.3145

Koh, 2016, From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites, Cell, 165, 1332, 10.1016/j.cell.2016.05.041

Kumar, 2016, MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets, Mol. Biol. Evol., 33, 1870, 10.1093/molbev/msw054

Larkin, 2007, Clustal W and Clustal X version 2.0, Bioinformatics, 23, 2947, 10.1093/bioinformatics/btm404

Layman, 2006, Potential importance of leucine in treatment of obesity and the metabolic syndrome, J. Nutr., 136, 319S, 10.1093/jn/136.1.319S

Le Chatelier, 2013, Richness of human gut microbiome correlates with metabolic markers, Nature, 500, 541, 10.1038/nature12506

Leontieva, 2014, Rapamycin reverses insulin resistance (IR) in high-glucose medium without causing IR in normoglycemic medium, Cell Death Dis., 5, e1214, 10.1038/cddis.2014.178

Linares, 2015, Amino acid activation of mTORC1 by a PB1-domain-driven kinase complex cascade, Cell Rep., 12, 1339, 10.1016/j.celrep.2015.07.045

Liu, 2017, Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention, Nat. Med., 23, 859, 10.1038/nm.4358

Love, 2014, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biol., 15, 550, 10.1186/s13059-014-0550-8

Mishima, 2017, Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach, Kidney Int., 92, 634, 10.1016/j.kint.2017.02.011

Mojtahedi, 2011, The effects of a higher protein intake during energy restriction on changes in body composition and physical function in older women, J. Gerontol. A Biol. Sci. Med. Sci., 66, 1218, 10.1093/gerona/glr120

Muto, 2006, Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis, Hepatol. Res., 35, 204

Ozes, 2001, A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1, Proc. Natl. Acad. Sci. USA, 98, 4640, 10.1073/pnas.051042298

Pedersen, 2016, Human gut microbes impact host serum metabolome and insulin sensitivity, Nature, 535, 376, 10.1038/nature18646

Qin, 2011, Higher branched-chain amino acid intake is associated with a lower prevalence of being overweight or obese in middle-aged East Asian and Western adults, J. Nutr., 141, 249, 10.3945/jn.110.128520

Qin, 2012, A metagenome-wide association study of gut microbiota in type 2 diabetes, Nature, 490, 55, 10.1038/nature11450

Ridaura, 2013, Gut microbiota from twins discordant for obesity modulate metabolism in mice, Science, 341, 1241214, 10.1126/science.1241214

Rui, 2001, Regulation of insulin/insulin-like growth factor-1 signaling by proteasome-mediated degradation of insulin receptor substrate-2, J. Biol. Chem., 276, 40362, 10.1074/jbc.M105332200

Sancak, 2008, The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1, Science, 320, 1496, 10.1126/science.1157535

Schröder, 1991, Identification of active site residues of Escherichia coli fumarate reductase by site-directed mutagenesis, J. Biol. Chem., 266, 13572, 10.1016/S0021-9258(18)92737-7

Schroeder, 2016, Signals from the gut microbiota to distant organs in physiology and disease, Nat. Med., 22, 1079, 10.1038/nm.4185

Shah, 2006, Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis, Mol. Cell. Biol., 26, 6425, 10.1128/MCB.01254-05

Shoaie, 2015, Quantifying diet-induced metabolic changes of the human gut microbiome, Cell Metab., 22, 320, 10.1016/j.cmet.2015.07.001

Smith, 2013, Gut microbiomes of Malawian twin pairs discordant for kwashiorkor, Science, 339, 548, 10.1126/science.1229000

Soliman, 2010, mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action, J. Biol. Chem., 285, 7866, 10.1074/jbc.M109.096222

Sonnenburg, 2016, Diet-microbiota interactions as moderators of human metabolism, Nature, 535, 56, 10.1038/nature18846

Suárez-Zamorano, 2015, Microbiota depletion promotes browning of white adipose tissue and reduces obesity, Nat. Med., 21, 1497, 10.1038/nm.3994

Tzatsos, 2009, Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR, J. Biol. Chem., 284, 22525, 10.1074/jbc.M109.027748

van der Heiden, 1972, Increased urinary imidazolepropionic acid, N-acetylhistamine and other imidazole compounds in patients with intestinal disorders, Clin. Chim. Acta, 39, 201, 10.1016/0009-8981(72)90317-8

Wallner, 2012, Catalytic and structural role of a conserved active site histidine in berberine bridge enzyme, Biochemistry, 51, 6139, 10.1021/bi300411n

Wang, 2005, Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins, Mol. Cell. Biol., 25, 2558, 10.1128/MCB.25.7.2558-2572.2005

Wang, 2011, Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease, Nature, 472, 57, 10.1038/nature09922

Windey, 2012, Relevance of protein fermentation to gut health, Mol. Nutr. Food Res., 56, 184, 10.1002/mnfr.201100542

Wu, 2017, Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug, Nat. Med., 23, 850, 10.1038/nm.4345

Yang, 2007, Expanding mTOR signaling, Cell Res., 17, 666, 10.1038/cr.2007.64

Zhang, 1993, Active site labeling of the Yersinia protein tyrosine phosphatase: the determination of the pKa of the active site cysteine and the function of the conserved histidine 402, Biochemistry, 32, 9340, 10.1021/bi00087a012

Zhang, 2007, Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms, Diabetes, 56, 1647, 10.2337/db07-0123

Zhang, 2012, PCB 126 and other dioxin-like PCBs specifically suppress hepatic PEPCK expression via the aryl hydrocarbon receptor, PLoS ONE, 7, e37103, 10.1371/journal.pone.0037103