{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:04:46Z","timestamp":1793898286533,"version":"4.8.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Metab"],"DOI":"10.1038\/s42255-021-00421-8","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T12:06:50Z","timestamp":1625141210000},"page":"923-939","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Intestinal MYC modulates obesity-related metabolic dysfunction"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-8380","authenticated-orcid":false,"given":"Yuhong","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoumei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3831-5353","authenticated-orcid":false,"given":"Shogo","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-5099","authenticated-orcid":false,"given":"Lulu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristopher W.","family":"Krausz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhen","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique B.","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Gavrilova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5206-2372","authenticated-orcid":false,"given":"Changtao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5069-9727","authenticated-orcid":false,"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-2140","authenticated-orcid":false,"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"421_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/nrgastro.2013.197","volume":"10","author":"K Ray","year":"2013","unstructured":"Ray, K. NAFLD\u2014the next global epidemic. Nat. Rev. Gastroenterol. Hepatol. 10, 621 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"421_CR2","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","volume":"15","author":"Z Younossi","year":"2018","unstructured":"Younossi, Z. et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 15, 11\u201320 (2018).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"421_CR3","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nrgastro.2013.41","volume":"10","author":"QM Anstee","year":"2013","unstructured":"Anstee, Q. M., Targher, G. & Day, C. P. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat. Rev. Gastroenterol. Hepatol. 10, 330\u2013344 (2013).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"421_CR4","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1002\/hep.26986","volume":"59","author":"RJ Wong","year":"2014","unstructured":"Wong, R. J., Cheung, R. & Ahmed, A. Non-alcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology 59, 2188\u20132195 (2014).","journal-title":"Hepatology"},{"key":"421_CR5","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","volume":"24","author":"SL Friedman","year":"2018","unstructured":"Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M. & Sanyal, A. J. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med. 24, 908\u2013922 (2018).","journal-title":"Nat. Med."},{"key":"421_CR6","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1038\/nrc2231","volume":"8","author":"N Meyer","year":"2008","unstructured":"Meyer, N. & Penn, L. Z. Reflecting on 25 years with MYC. Nat. Rev. Cancer 8, 976\u2013990 (2008).","journal-title":"Nat. Rev. Cancer"},{"key":"421_CR7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","volume":"149","author":"CV Dang","year":"2012","unstructured":"Dang, C. V. MYC on the path to cancer. Cell 149, 22\u201335 (2012).","journal-title":"Cell"},{"key":"421_CR8","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.jhep.2013.09.024","volume":"60","author":"A Qu","year":"2014","unstructured":"Qu, A. et al. Role of Myc in hepatocellular proliferation and hepatocarcinogenesis. J. Hepatol. 60, 331\u2013338 (2014).","journal-title":"J. Hepatol."},{"key":"421_CR9","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1038\/nature03043","volume":"431","author":"CM Shachaf","year":"2004","unstructured":"Shachaf, C. M. et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431, 1112\u20131117 (2004).","journal-title":"Nature"},{"key":"421_CR10","doi-asserted-by":"publisher","first-page":"6539","DOI":"10.1073\/pnas.1507228112","volume":"112","author":"EH Shroff","year":"2015","unstructured":"Shroff, E. H. et al. MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc. Natl Acad. Sci. USA 112, 6539\u20136544 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"421_CR11","doi-asserted-by":"publisher","first-page":"21797","DOI":"10.1074\/jbc.C000023200","volume":"275","author":"RC Osthus","year":"2000","unstructured":"Osthus, R. C. et al. Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc. J. Biol. Chem. 275, 21797\u201321800 (2000).","journal-title":"J. Biol. Chem."},{"key":"421_CR12","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.2741\/3848","volume":"16","author":"CW Peterson","year":"2011","unstructured":"Peterson, C. W. & Ayer, D. E. An extended Myc network contributes to glucose homeostasis in cancer and diabetes. Front. Biosci. 16, 2206\u20132223 (2011).","journal-title":"Front. Biosci."},{"key":"421_CR13","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.jhep.2015.11.005","volume":"64","author":"YA Nevzorova","year":"2016","unstructured":"Nevzorova, Y. A. et al. Enhanced expression of c-myc in hepatocytes promotes initiation and progression of alcoholic liver disease. J. Hepatol. 64, 628\u2013640 (2016).","journal-title":"J. Hepatol."},{"key":"421_CR14","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.celrep.2013.10.007","volume":"5","author":"J Shin","year":"2013","unstructured":"Shin, J. et al. SIRT7 represses myc activity to suppress ER stress and prevent fatty liver disease. Cell Rep. 5, 654\u2013665 (2013).","journal-title":"Cell Rep."},{"key":"421_CR15","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.cmet.2019.07.012","volume":"30","author":"AM Gouw","year":"2019","unstructured":"Gouw, A. M. et al. The MYC oncogene cooperates with sterol-regulated element-binding protein to regulate lipogenesis essential for neoplastic growth. Cell Metab. 30, 556\u2013572 e555 (2019).","journal-title":"Cell Metab."},{"key":"421_CR16","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1101\/gad.7.4.671","volume":"7","author":"AC Davis","year":"1993","unstructured":"Davis, A. C., Wims, M., Spotts, G. D., Hann, S. R. & Bradley, A. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Genes Dev. 7, 671\u2013682 (1993).","journal-title":"Genes Dev."},{"key":"421_CR17","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.cell.2014.12.016","volume":"160","author":"JW Hofmann","year":"2015","unstructured":"Hofmann, J. W. et al. Reduced expression of MYC increases longevity and enhances health span. Cell 160, 477\u2013488 (2015).","journal-title":"Cell"},{"key":"421_CR18","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1053\/j.gastro.2016.08.057","volume":"151","author":"FJ Gonzalez","year":"2016","unstructured":"Gonzalez, F. J., Jiang, C. & Patterson, A. D. An intestinal microbiota-farnesoid X receptor axis modulates metabolic disease. Gastroenterology 151, 845\u2013859 (2016).","journal-title":"Gastroenterology"},{"key":"421_CR19","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41574-018-0096-z","volume":"15","author":"FJ Gonzalez","year":"2018","unstructured":"Gonzalez, F. J., Xie, C. & Jiang, C. The role of hypoxia-inducible factors in metabolic diseases. Nat. Rev. Endocrinol. 15, 21\u201332 (2018).","journal-title":"Nat. Rev. Endocrinol."},{"key":"421_CR20","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.tem.2015.07.006","volume":"26","author":"B Chaurasia","year":"2015","unstructured":"Chaurasia, B. & Summers, S. A. Ceramides\u2014lipotoxic inducers of metabolic disorders. Trends Endocrinol. Metab. 26, 538\u2013550 (2015).","journal-title":"Trends Endocrinol. Metab."},{"key":"421_CR21","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.tem.2012.04.005","volume":"23","author":"M Pagadala","year":"2012","unstructured":"Pagadala, M., Kasumov, T., McCullough, A. J., Zein, N. N. & Kirwan, J. P. Role of ceramides in non-alcoholic fatty liver disease. Trends Endocrinol. Metab. 23, 365\u2013371 (2012).","journal-title":"Trends Endocrinol. Metab."},{"key":"421_CR22","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/j.cell.2012.02.017","volume":"148","author":"VT Samuel","year":"2012","unstructured":"Samuel, V. T. & Shulman, G. I. Mechanisms for insulin resistance: common threads and missing links. Cell 148, 852\u2013871 (2012).","journal-title":"Cell"},{"key":"421_CR23","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1038\/s42255-019-0134-8","volume":"1","author":"SA Summers","year":"2019","unstructured":"Summers, S. A., Chaurasia, B. & Holland, W. L. Metabolic Messengers: ceramides. Nat. Metab. 1, 1051\u20131058 (2019).","journal-title":"Nat. Metab."},{"key":"421_CR24","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nrm.2017.107","volume":"19","author":"YA Hannun","year":"2018","unstructured":"Hannun, Y. A. & Obeid, L. M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol. 19, 175\u2013191 (2018).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"421_CR25","doi-asserted-by":"publisher","first-page":"583","DOI":"10.2174\/1574888X14666190429143734","volume":"14","author":"SJ Liang","year":"2019","unstructured":"Liang, S. J., Li, X. G. & Wang, X. Q. Notch signaling in mammalian intestinal stem cells: determining cell fate and maintaining homeostasis. Curr. Stem Cell Res. Ther. 14, 583\u2013590 (2019).","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"421_CR26","doi-asserted-by":"publisher","first-page":"571","DOI":"10.15252\/embr.201540188","volume":"16","author":"R Sancho","year":"2015","unstructured":"Sancho, R., Cremona, C. A. & Behrens, A. Stem cell and progenitor fate in the mammalian intestine: Notch and lateral inhibition in homeostasis and disease. EMBO Rep. 16, 571\u2013581 (2015).","journal-title":"EMBO Rep."},{"key":"421_CR27","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/s41574-018-0016-2","volume":"14","author":"A Andersen","year":"2018","unstructured":"Andersen, A., Lund, A., Knop, F. K. & Vilsboll, T. Glucagon-like peptide 1 in health and disease. Nat. Rev. Endocrinol. 14, 390\u2013403 (2018).","journal-title":"Nat. Rev. Endocrinol."},{"key":"421_CR28","doi-asserted-by":"publisher","first-page":"187","DOI":"10.2337\/db11-1029","volume":"61","author":"V Gorboulev","year":"2012","unstructured":"Gorboulev, V. et al. Na+-d-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61, 187\u2013196 (2012).","journal-title":"Diabetes"},{"key":"421_CR29","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.2337\/diabetes.52.5.1147","volume":"52","author":"FM Gribble","year":"2003","unstructured":"Gribble, F. M., Williams, L., Simpson, A. K. & Reimann, F. A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line. Diabetes 52, 1147\u20131154 (2003).","journal-title":"Diabetes"},{"key":"421_CR30","doi-asserted-by":"publisher","first-page":"370","DOI":"10.2337\/db14-0807","volume":"64","author":"RE Kuhre","year":"2015","unstructured":"Kuhre, R. E., Frost, C. R., Svendsen, B. & Holst, J. J. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine. Diabetes 64, 370\u2013382 (2015).","journal-title":"Diabetes"},{"key":"421_CR31","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1007\/s00125-012-2585-2","volume":"55","author":"HE Parker","year":"2012","unstructured":"Parker, H. E. et al. Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion. Diabetologia 55, 2445\u20132455 (2012).","journal-title":"Diabetologia"},{"key":"421_CR32","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.cmet.2008.11.002","volume":"8","author":"F Reimann","year":"2008","unstructured":"Reimann, F. et al. Glucose sensing in L cells: a primary cell study. Cell Metab. 8, 532\u2013539 (2008).","journal-title":"Cell Metab."},{"key":"421_CR33","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.tem.2013.01.003","volume":"24","author":"G Filhoulaud","year":"2013","unstructured":"Filhoulaud, G., Guilmeau, S., Dentin, R., Girard, J. & Postic, C. Novel insights into ChREBP regulation and function. Trends Endocrinol. Metab. 24, 257\u2013268 (2013).","journal-title":"Trends Endocrinol. Metab."},{"key":"421_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8629","volume":"6","author":"MS Trabelsi","year":"2015","unstructured":"Trabelsi, M. S. et al. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat. Commun. 6, 7629 (2015).","journal-title":"Nat. Commun."},{"key":"421_CR35","doi-asserted-by":"publisher","first-page":"3736","DOI":"10.2337\/db13-0035","volume":"62","author":"J Mao","year":"2013","unstructured":"Mao, J. et al. Overnutrition stimulates intestinal epithelium proliferation through beta-catenin signaling in obese mice. Diabetes 62, 3736\u20133746 (2013).","journal-title":"Diabetes"},{"key":"421_CR36","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1194\/jlr.M600283-JLR200","volume":"48","author":"V Petit","year":"2007","unstructured":"Petit, V. et al. Chronic high-fat diet affects intestinal fat absorption and postprandial triglyceride levels in the mouse. J. Lipid Res. 48, 278\u2013287 (2007).","journal-title":"J. Lipid Res."},{"key":"421_CR37","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nature17173","volume":"531","author":"S Beyaz","year":"2016","unstructured":"Beyaz, S. et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531, 53\u201358 (2016).","journal-title":"Nature"},{"key":"421_CR38","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1126\/science.281.5382.1509","volume":"281","author":"TC He","year":"1998","unstructured":"He, T. C. et al. Identification of c-MYC as a target of the APC pathway. Science 281, 1509\u20131512 (1998).","journal-title":"Science"},{"key":"421_CR39","doi-asserted-by":"publisher","first-page":"7868","DOI":"10.1128\/MCB.25.17.7868-7878.2005","volume":"25","author":"MD Bettess","year":"2005","unstructured":"Bettess, M. D. et al. c-Myc is required for the formation of intestinal crypts but dispensable for homeostasis of the adult intestinal epithelium. Mol. Cell. Biol. 25, 7868\u20137878 (2005).","journal-title":"Mol. Cell. Biol."},{"key":"421_CR40","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1146\/annurev-physiol-021113-170315","volume":"76","author":"YM Cho","year":"2014","unstructured":"Cho, Y. M., Fujita, Y. & Kieffer, T. J. Glucagon-like peptide-1: glucose homeostasis and beyond. Annu. Rev. Physiol. 76, 535\u2013559 (2014).","journal-title":"Annu. Rev. Physiol."},{"key":"421_CR41","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1007\/BF00401145","volume":"36","author":"MA Nauck","year":"1993","unstructured":"Nauck, M. A. et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 741\u2013744 (1993).","journal-title":"Diabetologia"},{"key":"421_CR42","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s001250050664","volume":"40","author":"J Rachman","year":"1997","unstructured":"Rachman, J., Barrow, B. A., Levy, J. C. & Turner, R. C. Near-normalisation of diurnal glucose concentrations by continuous administration of glucagon-like peptide-1 (GLP-1) in subjects with NIDDM. Diabetologia 40, 205\u2013211 (1997).","journal-title":"Diabetologia"},{"key":"421_CR43","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","volume":"87","author":"JJ Holst","year":"2007","unstructured":"Holst, J. J. The physiology of glucagon-like peptide 1. Physiol. Rev. 87, 1409\u20131439 (2007).","journal-title":"Physiol. Rev."},{"key":"421_CR44","doi-asserted-by":"publisher","first-page":"530","DOI":"10.2337\/diabetes.47.4.530","volume":"47","author":"M Tang-Christensen","year":"1998","unstructured":"Tang-Christensen, M., Vrang, N. & Larsen, P. J. Glucagon-like peptide 1(7-36) amide\u2019s central inhibition of feeding and peripheral inhibition of drinking are abolished by neonatal monosodium glutamate treatment. Diabetes 47, 530\u2013537 (1998).","journal-title":"Diabetes"},{"key":"421_CR45","first-page":"4382","volume":"86","author":"C Verdich","year":"2001","unstructured":"Verdich, C. et al. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J. Clin. Endocrinol. Metab. 86, 4382\u20134389 (2001).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"421_CR46","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.cmet.2017.12.003","volume":"27","author":"SA Summers","year":"2018","unstructured":"Summers, S. A. Could ceramides become the new cholesterol? Cell Metab. 27, 276\u2013280 (2018).","journal-title":"Cell Metab."},{"key":"421_CR47","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1194\/jlr.P056002","volume":"56","author":"DL Gorden","year":"2015","unstructured":"Gorden, D. L. et al. Biomarkers of NAFLD progression: a lipidomics approach to an epidemic. J. Lipid Res. 56, 722\u2013736 (2015).","journal-title":"J. Lipid Res."},{"key":"421_CR48","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1093\/eurheartj\/ehw148","volume":"37","author":"R Laaksonen","year":"2016","unstructured":"Laaksonen, R. et al. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL cholesterol. Eur. Heart J. 37, 1967\u20131976 (2016).","journal-title":"Eur. Heart J."},{"key":"421_CR49","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1021\/pr5009898","volume":"14","author":"PA Vorkas","year":"2015","unstructured":"Vorkas, P. A. et al. Metabolic phenotyping of atherosclerotic plaques reveals latent associations between free cholesterol and ceramide metabolism in atherogenesis. J. Proteome Res. 14, 1389\u20131399 (2015).","journal-title":"J. Proteome Res."},{"key":"421_CR50","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.cmet.2012.04.002","volume":"15","author":"JA Chavez","year":"2012","unstructured":"Chavez, J. A. & Summers, S. A. A ceramide-centric view of insulin resistance. Cell Metab. 15, 585\u2013594 (2012).","journal-title":"Cell Metab."},{"key":"421_CR51","doi-asserted-by":"publisher","first-page":"337","DOI":"10.2337\/db08-1228","volume":"58","author":"JM Haus","year":"2009","unstructured":"Haus, J. M. et al. Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58, 337\u2013343 (2009).","journal-title":"Diabetes"},{"key":"421_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-1-12","volume":"1","author":"L Yetukuri","year":"2007","unstructured":"Yetukuri, L. et al. Bioinformatics strategies for lipidomics analysis: characterization of obesity-related hepatic steatosis. BMC Syst. Biol. 1, 12 (2007).","journal-title":"BMC Syst. Biol."},{"key":"421_CR53","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1172\/JCI76738","volume":"125","author":"C Jiang","year":"2015","unstructured":"Jiang, C. et al. Intestinal farnesoid X receptor signaling promotes non-alcoholic fatty liver disease. J. Clin. Invest. 125, 386\u2013402 (2015).","journal-title":"J. Clin. Invest."},{"key":"421_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10166","volume":"6","author":"C Jiang","year":"2015","unstructured":"Jiang, C. et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat. Commun. 6, 10166 (2015).","journal-title":"Nat. Commun."},{"key":"421_CR55","doi-asserted-by":"publisher","first-page":"613","DOI":"10.2337\/db16-0663","volume":"66","author":"C Xie","year":"2017","unstructured":"Xie, C. et al. An intestinal farnesoid X receptor-ceramide signaling axis modulates hepatic gluconeogenesis in mice. Diabetes 66, 613\u2013626 (2017).","journal-title":"Diabetes"},{"key":"421_CR56","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.cmet.2019.09.016","volume":"30","author":"X Zhang","year":"2019","unstructured":"Zhang, X. et al. Adipocyte hypoxia-inducible factor 2\u03b1 suppresses atherosclerosis by promoting adipose ceramide catabolism. Cell Metab. 30, 937\u2013951 (2019).","journal-title":"Cell Metab."},{"key":"421_CR57","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/j.cmet.2016.10.002","volume":"24","author":"B Chaurasia","year":"2016","unstructured":"Chaurasia, B. et al. Adipocyte ceramides regulate subcutaneous adipose browning, inflammation and metabolism. Cell Metab. 24, 820\u2013834 (2016).","journal-title":"Cell Metab."},{"key":"421_CR58","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.cmet.2014.08.002","volume":"20","author":"SM Turpin","year":"2014","unstructured":"Turpin, S. M. et al. Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metab. 20, 678\u2013686 (2014).","journal-title":"Cell Metab."},{"key":"421_CR59","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.plipres.2016.03.006","volume":"63","author":"MS Wegner","year":"2016","unstructured":"Wegner, M. S., Schiffmann, S., Parnham, M. J., Geisslinger, G. & Grosch, S. The enigma of ceramide synthase regulation in mammalian cells. Prog. Lipid Res. 63, 93\u2013119 (2016).","journal-title":"Prog. Lipid Res."},{"key":"421_CR60","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1016\/j.biocel.2013.06.004","volume":"45","author":"S Schiffmann","year":"2013","unstructured":"Schiffmann, S. et al. Ceramide metabolism in mouse tissue. Int. J. Biochem. Cell Biol. 45, 1886\u20131894 (2013).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"421_CR61","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1038\/jid.2015.60","volume":"135","author":"F Peters","year":"2015","unstructured":"Peters, F. et al. Ceramide synthase 4 regulates stem cell homeostasis and hair follicle cycling. J. Invest. Dermatol. 135, 1501\u20131509 (2015).","journal-title":"J. Invest. Dermatol."},{"key":"421_CR62","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1042\/BJ20050291","volume":"390","author":"Y Mizutani","year":"2005","unstructured":"Mizutani, Y., Kihara, A. & Igarashi, Y. Mammalian Lass6 and its related family members regulate synthesis of specific ceramides. Biochem. J. 390, 263\u2013271 (2005).","journal-title":"Biochem. J."},{"key":"421_CR63","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fcell.2017.00010","volume":"5","author":"JR Whitfield","year":"2017","unstructured":"Whitfield, J. R., Beaulieu, M. E. & Soucek, L. Strategies to inhibit myc and their clinical applicability. Front Cell Dev. Biol. 5, 10 (2017).","journal-title":"Front Cell Dev. Biol."},{"key":"421_CR64","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s00280-008-0774-y","volume":"63","author":"J Guo","year":"2009","unstructured":"Guo, J. et al. Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc\u2013Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice. Cancer Chemother. Pharmacol. 63, 615\u2013625 (2009).","journal-title":"Cancer Chemother. Pharmacol."},{"key":"421_CR65","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/S1074-7613(01)00088-7","volume":"14","author":"IM de Alboran","year":"2001","unstructured":"de Alboran, I. M. et al. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14, 45\u201355 (2001).","journal-title":"Immunity"},{"key":"421_CR66","doi-asserted-by":"publisher","first-page":"33275","DOI":"10.1074\/jbc.M204935200","volume":"277","author":"BB Madison","year":"2002","unstructured":"Madison, B. B. et al. Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine. J. Biol. Chem. 277, 33275\u201333283 (2002).","journal-title":"J. Biol. Chem."},{"key":"421_CR67","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1002\/gene.20042","volume":"39","author":"F el Marjou","year":"2004","unstructured":"el Marjou, F. et al. Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39, 186\u2013193 (2004).","journal-title":"Genesis"},{"key":"421_CR68","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1126\/science.1164270","volume":"322","author":"K Okita","year":"2008","unstructured":"Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T. & Yamanaka, S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 322, 949\u2013953 (2008).","journal-title":"Science"},{"key":"421_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","volume":"37","author":"W Huang da","year":"2009","unstructured":"Huang da, W., Sherman, B. T. & Lempicki, R. A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37, 1\u201313 (2009).","journal-title":"Nucleic Acids Res."},{"key":"421_CR70","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"W Huang da","year":"2009","unstructured":"Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44\u201357 (2009).","journal-title":"Nat. Protoc."}],"container-title":["Nature Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42255-021-00421-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-021-00421-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-021-00421-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T15:32:48Z","timestamp":1670081568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42255-021-00421-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":70,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["421"],"URL":"https:\/\/doi.org\/10.1038\/s42255-021-00421-8","relation":{},"ISSN":["2522-5812"],"issn-type":[{"value":"2522-5812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]},"assertion":[{"value":"26 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}