{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:38:14Z","timestamp":1785447494952,"version":"3.56.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI150462"],"award-info":[{"award-number":["AI150462"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI123105"],"award-info":[{"award-number":["AI123105"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetes mellitus (DM) is associated with a dysfunctional intestinal barrier and an increased risk for systemic infection and inflammation in people, though the pathogenic mechanisms leading to this are poorly understood. Using a canine model of DM, we showed that the peroxisomal proliferator-activated receptor-\u03b1 agonist fenofibrate modulates plasma lipid profiles and markers of intestinal barrier function. A 3-week course of fenofibrate reduced fasting interstitial glucose and inflammatory cytokine IL-8 and TNF-\u03b1 concentrations, which correlated with reduced triglyceride levels. The lipidomic profile exhibited significantly lower levels of triacylglycerols, phosphatidylethanolamines, diacylglycerols, and ceramides following fenofibrate administration. On histopathological analysis, we observed an aberrant amount of intraepithelial CD3<jats:sup>+<\/jats:sup>T lymphocytes (IEL) in the small intestine of dogs with spontaneous and induced-DM. Fenofibrate reduced IEL density in the duodenum of dogs with DM and enhanced markers of intestinal barrier function in vivo and in vitro<jats:italic>.<\/jats:italic>There were minimal changes in the intestinal microbial composition following fenofibrate administration, suggesting that repair of intestinal barriers can be achieved independently of the resident microbiota. Our findings indicate that lipid metabolism is critical to functionality of the intestinal epithelium, which can be rescued by PPAR\u03b1 activation in dogs with DM.<\/jats:p>","DOI":"10.1038\/s41598-021-92966-7","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:06:39Z","timestamp":1624961199000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Fenofibrate promotes PPAR\u03b1-targeted recovery of the intestinal epithelial barrier at the host-microbe interface in dogs with diabetes mellitus"],"prefix":"10.1038","volume":"11","author":[{"given":"Katti R.","family":"Crakes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jully","family":"Pires","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Quach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley E.","family":"Ellis-Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Greathouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathyrnne A.","family":"Chittum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg M.","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Pesavento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley L.","family":"Marks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya","family":"Dandekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Gilor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"92966_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.cmet.2016.01.003","volume":"23","author":"DA Winer","year":"2016","unstructured":"Winer, D. A., Luck, H., Tsai, S. & Winer, S. The intestinal immune system in obesity and insulin resistance. Cell Metab. 23, 413\u2013426 (2016).","journal-title":"Cell Metab."},{"key":"92966_CR2","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.clnu.2012.02.009","volume":"31","author":"TF Teixeira","year":"2012","unstructured":"Teixeira, T. F. et al. Intestinal permeability parameters in obese patients are correlated with metabolic syndrome risk factors. Clin. Nutr. 31, 735\u2013740 (2012).","journal-title":"Clin. Nutr."},{"key":"92966_CR3","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.cmet.2015.07.026","volume":"22","author":"R Caesar","year":"2015","unstructured":"Caesar, R., Tremaroli, V., Kovatcheva-Datchary, P., Cani, P. D. & Backhed, F. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 22, 658\u2013668 (2015).","journal-title":"Cell Metab."},{"key":"92966_CR4","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1097\/EDE.0000000000000301","volume":"26","author":"KA Kaspersen","year":"2015","unstructured":"Kaspersen, K. A. et al. Obesity and risk of infection: Results from the Danish Blood Donor Study. Epidemiology 26, 580\u2013589 (2015).","journal-title":"Epidemiology"},{"key":"92966_CR5","doi-asserted-by":"publisher","first-page":"4050","DOI":"10.1172\/JCI129194","volume":"129","author":"K Dabke","year":"2019","unstructured":"Dabke, K., Hendrick, G. & Devkota, S. The gut microbiome and metabolic syndrome. J. Clin. Invest. 129, 4050\u20134057 (2019).","journal-title":"J. Clin. Invest."},{"key":"92966_CR6","doi-asserted-by":"publisher","first-page":"24819","DOI":"10.1073\/pnas.1908977116","volume":"116","author":"KR Crakes","year":"2019","unstructured":"Crakes, K. R. et al. PPAR\u03b1-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host\u2013microbe intersection during SIV infection. Proc. Natl. Acad. Sci. 116, 24819 (2019).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"92966_CR7","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1210\/endo.137.1.8536636","volume":"137","author":"O Braissant","year":"1996","unstructured":"Braissant, O., Foufelle, F., Scotto, C., Dauca, M. & Wahli, W. Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 137, 354\u2013366 (1996).","journal-title":"Endocrinology"},{"key":"92966_CR8","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1136\/gutjnl-2015-310798","volume":"65","author":"A Montagner","year":"2016","unstructured":"Montagner, A. et al. Liver PPAR\u03b1 is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut 65, 1202 (2016).","journal-title":"Gut"},{"key":"92966_CR9","doi-asserted-by":"publisher","first-page":"16638","DOI":"10.1074\/jbc.275.22.16638","volume":"275","author":"M Guerre-Millo","year":"2000","unstructured":"Guerre-Millo, M. et al. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J. Biol. Chem. 275, 16638\u201316642 (2000).","journal-title":"J. Biol. Chem."},{"key":"92966_CR10","doi-asserted-by":"publisher","first-page":"411","DOI":"10.2337\/diabetes.50.2.411","volume":"50","author":"J-M Ye","year":"2001","unstructured":"Ye, J.-M. et al. Peroxisome proliferator-activated receptor (PPAR)-\u03b1 activation lowers muscle lipids and improves insulin sensitivity in high fat-fed rats. Diabetes 50, 411 (2001).","journal-title":"Diabetes"},{"key":"92966_CR11","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.2337\/db06-0016","volume":"55","author":"F Lalloyer","year":"2006","unstructured":"Lalloyer, F. et al. Peroxisome proliferator-activated receptor alpha improves pancreatic adaptation to insulin resistance in obese mice and reduces lipotoxicity in human islets. Diabetes 55, 1605\u20131613 (2006).","journal-title":"Diabetes"},{"key":"92966_CR12","doi-asserted-by":"publisher","first-page":"493","DOI":"10.2337\/dc08-1543","volume":"32","author":"R Scott","year":"2009","unstructured":"Scott, R. et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care 32, 493\u2013498 (2009).","journal-title":"Diabetes Care"},{"key":"92966_CR13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4049\/jimmunol.202.Supp.178.8","volume":"202","author":"M Falcone","year":"2019","unstructured":"Falcone, M. et al. Loss of gut barrier integrity triggers autoimmune diabetes through microbiota-induced activation of islet-reactive T cells. J. Immunol. 202, 178 (2019).","journal-title":"J. Immunol."},{"key":"92966_CR14","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLOS Biol. 18, e3000410 (2020).","journal-title":"PLOS Biol."},{"key":"92966_CR15","doi-asserted-by":"publisher","first-page":"19187","DOI":"10.1038\/s41598-020-76091-5","volume":"10","author":"C Gilor","year":"2020","unstructured":"Gilor, C. et al. Loss of sympathetic innervation to islets of Langerhans in canine diabetes and pancreatitis is not associated with insulitis. Sci. Rep. 10, 19187 (2020).","journal-title":"Sci. Rep."},{"key":"92966_CR16","unstructured":"Endocrinology, E. S. O. V. E. A. S. F. C. Project ALIVE: Agreeing language in Veterinary Endocrinology. 2016; Available from: https:\/\/www.esve.org\/alive\/intro.aspx."},{"key":"92966_CR17","unstructured":"Edward Feldman, R. N., Claudia Reusc, J. Catharine Scott-Moncrieff, Canine and feline endocrinology 4th ed., ed. Saunders. 2014. 688."},{"key":"92966_CR18","doi-asserted-by":"publisher","first-page":"106578","DOI":"10.1016\/j.domaniend.2020.106578","volume":"74","author":"DD Miceli","year":"2021","unstructured":"Miceli, D. D., Vidal, V. P., Blatter, M. F. C., Pignataro, O. P. & Castillo, V. A. Fenofibrate treatment for severe hypertriglyceridemia in dogs. Domest. Anim. Endocrinol. 74, 106578 (2021).","journal-title":"Domest. Anim. Endocrinol."},{"key":"92966_CR19","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1111\/jvim.14355","volume":"30","author":"S Corradini","year":"2016","unstructured":"Corradini, S. et al. Accuracy of a flash glucose monitoring system in diabetic dogs. J. Vet. Intern. Med. 30, 983\u2013988 (2016).","journal-title":"J. Vet. Intern. Med."},{"key":"92966_CR20","doi-asserted-by":"publisher","first-page":"105379","DOI":"10.1016\/j.tvjl.2019.105379","volume":"253","author":"C Muller","year":"2019","unstructured":"Muller, C., Enomoto, M., Buono, A., Steiner, J. M. & Lascelles, B. D. X. Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis. Vet. J. 253, 105379 (2019).","journal-title":"Vet. J."},{"key":"92966_CR21","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/nmeth.3393","volume":"12","author":"H Tsugawa","year":"2015","unstructured":"Tsugawa, H. et al. MS-DIAL: Data-independent MS\/MS deconvolution for comprehensive metabolome analysis. Nat. Methods 12, 523\u2013526 (2015).","journal-title":"Nat. Methods"},{"issue":"Suppl 1","key":"92966_CR22","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.jcpa.2008.01.001","volume":"138","author":"MJ Day","year":"2008","unstructured":"Day, M. J. et al. Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: A report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group. J. Comp. Pathol. 138(Suppl 1), S1-43 (2008).","journal-title":"J. Comp. Pathol."},{"key":"92966_CR23","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1053\/j.gastro.2020.07.003","volume":"159","author":"I Grosheva","year":"2020","unstructured":"Grosheva, I. et al. High-throughput screen identifies host and microbiota regulators of intestinal barrier function. Gastroenterology 159, 1807\u20131823 (2020).","journal-title":"Gastroenterology"},{"key":"92966_CR24","doi-asserted-by":"publisher","first-page":"e4827","DOI":"10.7717\/peerj.4827","volume":"6","author":"KR Horng","year":"2018","unstructured":"Horng, K. R., Ganz, H. H., Eisen, J. A. & Marks, S. L. Effects of preservation method on canine (Canis lupus familiaris) fecal microbiota. PeerJ 6, e4827 (2018).","journal-title":"PeerJ"},{"key":"92966_CR25","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, Austria. (2020)."},{"key":"92966_CR26","doi-asserted-by":"publisher","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","volume":"8","author":"PJ McMurdie","year":"2013","unstructured":"McMurdie, P. J. & Holmes, S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217 (2013).","journal-title":"PLoS ONE"},{"key":"92966_CR27","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"92966_CR28","doi-asserted-by":"publisher","first-page":"e00129","DOI":"10.1128\/MRA.00129-19","volume":"8","author":"CR Tiffany","year":"2019","unstructured":"Tiffany, C. R. & Baumler, A. J. omu, a metabolomics count data analysis tool for intuitive figures and convenient metadata collection. Microbiol. Resour. Announc. 8, e00129 (2019).","journal-title":"Microbiol. Resour. Announc."},{"key":"92966_CR29","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1939-1676.2007.0001.x","volume":"22","author":"CE Wiedmeyer","year":"2008","unstructured":"Wiedmeyer, C. E. & DeClue, A. E. Continuous glucose monitoring in dogs and cats. J. Vet. Intern. Med.. 22, 2\u20138 (2008).","journal-title":"J. Vet. Intern. Med.."},{"key":"92966_CR30","doi-asserted-by":"publisher","first-page":"2024s","DOI":"10.1093\/jn\/136.7.2024S","volume":"136","author":"RC Hill","year":"2006","unstructured":"Hill, R. C. et al. Texturized vegetable protein containing indigestible soy carbohydrate affects blood insulin concentrations in dogs fed high fat diets. J. Nutr. 136, 2024s\u20132027s (2006).","journal-title":"J. Nutr."},{"key":"92966_CR31","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1111\/j.1439-0396.2007.00794.x","volume":"92","author":"AC Carciofi","year":"2008","unstructured":"Carciofi, A. C. et al. Effects of six carbohydrate sources on dog diet digestibility and post-prandial glucose and insulin response. J. Anim. Physiol. Anim. Nutr. (Ber). 92, 326\u2013336 (2008).","journal-title":"J. Anim. Physiol. Anim. Nutr. (Ber)."},{"key":"92966_CR32","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.rvsc.2011.07.032","volume":"93","author":"KF Elliott","year":"2012","unstructured":"Elliott, K. F. et al. A diet lower in digestible carbohydrate results in lower postprandial glucose concentrations compared with a traditional canine diabetes diet and an adult maintenance diet in healthy dogs. Res. Vet. Sci. 93, 288\u2013295 (2012).","journal-title":"Res. Vet. Sci."},{"key":"92966_CR33","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1053\/j.gastro.2014.09.037","volume":"148","author":"Q Zhou","year":"2015","unstructured":"Zhou, Q. et al. MicroRNA 29 targets nuclear factor-\u03baB-repressing factor and Claudin 1 to increase intestinal permeability. Gastroenterology 148, 158-169.e158 (2015).","journal-title":"Gastroenterology"},{"key":"92966_CR34","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1126\/science.aar3318","volume":"359","author":"CA Thaiss","year":"2018","unstructured":"Thaiss, C. A. et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science 359, 1376 (2018).","journal-title":"Science"},{"key":"92966_CR35","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1939-1676.2010.0520.x","volume":"24","author":"RJ Washabau","year":"2010","unstructured":"Washabau, R. J. et al. Endoscopic, biopsy, and histopathologic guidelines for the evaluation of gastrointestinal inflammation in companion animals. J. Vet. Intern. Med. 24, 10\u201326 (2010).","journal-title":"J. Vet. Intern. Med."},{"key":"92966_CR36","doi-asserted-by":"publisher","first-page":"e00163","DOI":"10.1128\/mSystems.00163-18","volume":"4","author":"V Caruso","year":"2019","unstructured":"Caruso, V., Song, X., Asquith, M. & Karstens, L. Performance of microbiome sequence inference methods in environments with varying biomass. mSystems 4, e00163-e118 (2019).","journal-title":"mSystems"},{"key":"92966_CR37","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1126\/science.aat0835","volume":"359","author":"S Citi","year":"2018","unstructured":"Citi, S. Intestinal barriers protect against disease. Science 359, 1097\u20131098 (2018).","journal-title":"Science"},{"key":"92966_CR38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s12276-018-0126-x","volume":"50","author":"C Chelakkot","year":"2018","unstructured":"Chelakkot, C., Ghim, J. & Ryu, S. H. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp. Mol. Med. 50, 103\u2013103 (2018).","journal-title":"Exp. Mol. Med."},{"key":"92966_CR39","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.it.2014.08.002","volume":"35","author":"GE Kaiko","year":"2014","unstructured":"Kaiko, G. E. & Stappenbeck, T. S. Host-microbe interactions shaping the gastrointestinal environment. Trends Immunol. 35, 538\u2013548 (2014).","journal-title":"Trends Immunol."},{"key":"92966_CR40","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1136\/gutjnl-2014-308778","volume":"65","author":"MC Dao","year":"2016","unstructured":"Dao, M. C. et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65, 426\u2013436 (2016).","journal-title":"Gut"},{"key":"92966_CR41","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1038\/nrendo.2017.161","volume":"14","author":"M Kleinert","year":"2018","unstructured":"Kleinert, M. et al. Animal models of obesity and diabetes mellitus. Nat. Rev. Endocrinol. 14, 140\u2013162 (2018).","journal-title":"Nat. Rev. Endocrinol."},{"key":"92966_CR42","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.2337\/db16-1551","volume":"66","author":"AL O'Kell","year":"2017","unstructured":"O\u2019Kell, A. L. et al. Comparative pathogenesis of autoimmune diabetes in humans, NOD mice, and canines: Has a valuable animal model of Type 1 Diabetes been overlooked?. Diabetes 66, 1443\u20131452 (2017).","journal-title":"Diabetes"},{"key":"92966_CR43","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.2337\/diacare.25.8.1410","volume":"25","author":"S Colagiuri","year":"2002","unstructured":"Colagiuri, S., Cull, C. A. & Holman, R. R. Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcomes?. Diabetes Care 25, 1410 (2002).","journal-title":"Diabetes Care"},{"key":"92966_CR44","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.2337\/dc12-1577","volume":"36","author":"C Park","year":"2013","unstructured":"Park, C. et al. Fasting glucose level and the risk of incident atherosclerotic cardiovascular diseases. Diabetes Care 36, 1988\u20131993 (2013).","journal-title":"Diabetes Care"},{"key":"92966_CR45","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1111\/j.1600-0463.2005.apm_204.x","volume":"113","author":"F Chang","year":"2005","unstructured":"Chang, F., Mahadeva, U. L. A. & Deere, H. Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa. APMIS 113, 385\u2013399 (2005).","journal-title":"APMIS"},{"key":"92966_CR46","doi-asserted-by":"publisher","first-page":"15140","DOI":"10.1073\/pnas.1814558116","volume":"116","author":"C Sorini","year":"2019","unstructured":"Sorini, C. et al. Loss of gut barrier integrity triggers activation of islet-reactive T cells and autoimmune diabetes. Proc. Natl. Acad. Sci. 116, 15140 (2019).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"92966_CR47","doi-asserted-by":"publisher","first-page":"R225","DOI":"10.1530\/JME-16-0249","volume":"58","author":"RH Ritchie","year":"2017","unstructured":"Ritchie, R. H., Zerenturk, E. J., Prakoso, D. & Calkin, A. C. Lipid metabolism and its implications for type 1 diabetes-associated cardiomyopathy. J. Mol. Endocrinol. 58, R225-r240 (2017).","journal-title":"J. Mol. Endocrinol."},{"key":"92966_CR48","doi-asserted-by":"publisher","first-page":"384","DOI":"10.3389\/fendo.2018.00384","volume":"9","author":"YS Oh","year":"2018","unstructured":"Oh, Y. S., Bae, G. D., Baek, D. J., Park, E.-Y. & Jun, H.-S. Fatty acid-induced lipotoxicity in pancreatic beta-cells during development of Type 2 Diabetes. Front. Endocrinol. 9, 384\u2013384 (2018).","journal-title":"Front. Endocrinol."},{"key":"92966_CR49","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/j.clinbiochem.2010.04.075","volume":"43","author":"CM Sorensen","year":"2010","unstructured":"Sorensen, C. M. et al. Perturbations in the lipid profile of individuals with newly diagnosed type 1 diabetes mellitus: Lipidomics analysis of a Diabetes Antibody Standardization Program sample subset. Clin. Biochem. 43, 948\u2013956 (2010).","journal-title":"Clin. Biochem."},{"key":"92966_CR50","doi-asserted-by":"publisher","first-page":"16398","DOI":"10.1038\/s41598-019-52916-w","volume":"9","author":"N Tofte","year":"2019","unstructured":"Tofte, N. et al. Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes. Sci. Rep. 9, 16398 (2019).","journal-title":"Sci. Rep."},{"key":"92966_CR51","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1007\/s00125-018-4614-2","volume":"61","author":"LJ Holm","year":"2018","unstructured":"Holm, L. J. et al. Abnormal islet sphingolipid metabolism in type 1 diabetes. Diabetologia 61, 1650\u20131661 (2018).","journal-title":"Diabetologia"},{"key":"92966_CR52","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1161\/01.ATV.16.6.763","volume":"16","author":"M Gu\u00e9rin","year":"1996","unstructured":"Gu\u00e9rin, M., Bruckert, E., Dolphin, P. J., Turpin, G. & Chapman, M. J. Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia. Arterioscler. Thromb. Vasc. Biol. 16, 763\u2013772 (1996).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"92966_CR53","doi-asserted-by":"publisher","first-page":"9467","DOI":"10.1038\/s41598-017-09908-5","volume":"7","author":"AL O'Kell","year":"2017","unstructured":"O\u2019Kell, A. L., Garrett, T. J., Wasserfall, C. & Atkinson, M. A. Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes. Sci. Rep. 7, 9467\u20139467 (2017).","journal-title":"Sci. Rep."},{"key":"92966_CR54","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.bbalip.2010.12.011","volume":"1811","author":"A Uchida","year":"2011","unstructured":"Uchida, A., Slipchenko, M. N., Cheng, J.-X. & Buhman, K. K. Fenofibrate, a peroxisome proliferator-activated receptor \u03b1 agonist, alters triglyceride metabolism in enterocytes of mice. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1811, 170\u2013176 (2011).","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"92966_CR55","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1007\/s00383-016-3979-x","volume":"32","author":"I Sukhotnik","year":"2016","unstructured":"Sukhotnik, I. et al. Fenofibrate reduces intestinal damage and improves intestinal recovery following intestinal ischemia\u2013reperfusion injury in a rat. Ped. Surg. Intt. 32, 1193\u20131200 (2016).","journal-title":"Ped. Surg. Intt."},{"key":"92966_CR56","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s00281-019-00747-2","volume":"41","author":"LL Lehrskov","year":"2019","unstructured":"Lehrskov, L. L. & Christensen, R. H. The role of interleukin-6 in glucose homeostasis and lipid metabolism. Semin. Immunopathol. 41, 491\u2013499 (2019).","journal-title":"Semin. Immunopathol."},{"key":"92966_CR57","doi-asserted-by":"publisher","first-page":"S28","DOI":"10.1038\/ijosup.2016.6","volume":"6","author":"PD Cani","year":"2016","unstructured":"Cani, P. D. Interactions between gut microbes and host cells control gut barrier and metabolism. Int. J. Obes. Suppl. 6, S28\u2013S31 (2016).","journal-title":"Int. J. Obes. Suppl."},{"key":"92966_CR58","doi-asserted-by":"publisher","first-page":"e970940","DOI":"10.4161\/21688362.2014.970940","volume":"2","author":"G Le Drean","year":"2014","unstructured":"Le Drean, G. & Segain, J. P. Connecting metabolism to intestinal barrier function: The role of leptin. Tissue Barriers 2, e970940 (2014).","journal-title":"Tissue Barriers"},{"key":"92966_CR59","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.3390\/ijms19061575","volume":"19","author":"G Le Menn","year":"2018","unstructured":"Le Menn, G. & Neels, J. G. Regulation of immune cell function by PPARs and the connection with metabolic and neurodegenerative diseases. Int. J. Mol. Sci. 19, 1575 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"92966_CR60","doi-asserted-by":"publisher","first-page":"199","DOI":"10.3389\/fvets.2019.00199","volume":"6","author":"AE Jergens","year":"2019","unstructured":"Jergens, A. E. et al. Microbiota-related changes in unconjugated fecal bile acids are associated with naturally occurring, insulin-dependent diabetes mellitus in dogs. Front. Vet. Sci. 6, 199 (2019).","journal-title":"Front. Vet. Sci."},{"key":"92966_CR61","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1007\/s00335-007-9037-1","volume":"18","author":"KL Tsai","year":"2007","unstructured":"Tsai, K. L., Clark, L. A. & Murphy, K. E. Understanding hereditary diseases using the dog and human as companion model systems. Mamm. Genome 18, 444\u2013451 (2007).","journal-title":"Mamm. Genome"},{"key":"92966_CR62","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/nbt0906-1065b","volume":"24","author":"C Khanna","year":"2006","unstructured":"Khanna, C. et al. The dog as a cancer model. Nat. Biotechnol. 24, 1065\u20131066 (2006).","journal-title":"Nat. Biotechnol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92966-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92966-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92966-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T23:08:29Z","timestamp":1672614509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92966-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["92966"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-92966-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]},"assertion":[{"value":"27 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 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"}}],"article-number":"13454"}}