{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:27:22Z","timestamp":1791289642882,"version":"4.3.0"},"reference-count":137,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Guelph - Ontario Veterinary College - Pet Trust Foundation","award":["054460"],"award-info":[{"award-number":["054460"]}]},{"name":"University of Guelph - Ontario Veterinary College - Pet Trust Foundation","award":["054460"],"award-info":[{"award-number":["054460"]}]},{"name":"University of Guelph - Ontario Veterinary College - Pet Trust Foundation","award":["054460"],"award-info":[{"award-number":["054460"]}]},{"name":"University of Guelph - Ontario Veterinary College - Pet Trust Foundation","award":["054460"],"award-info":[{"award-number":["054460"]}]},{"name":"University of Guelph - Ontario Veterinary College - Pet Trust Foundation","award":["054460"],"award-info":[{"award-number":["054460"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Objectives<\/jats:title><jats:p>To evaluate the association between plasma metabolites, biochemical analytes, diagnostic imaging findings, and the histologic diagnosis of hepatic lipidosis in bearded dragons. To assess the effects of gemfibrozil therapy on hepatic lipid accumulation and associated diagnostic tests.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Animals<\/jats:title><jats:p>Fourteen bearded dragons (<jats:italic>Pogona vitticeps)<\/jats:italic>with varying severity of hepatic lipid accumulation (with and without hepatic lipidosis) were included.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Procedures<\/jats:title><jats:p>Animals underwent coelomic ultrasound, computed tomography (CT) scans, and coelioscopic hepatic biopsies. Clinical pathology tests included lipidologic tests, hepatic biomarkers, and mass spectrometry-based metabolomics. Animals were medicated with gemfibrozil 6mg\/kg orally once a day for 2 months in a randomized blinded clinical trial prior to repeating previous diagnostic testing.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Results<\/jats:title><jats:p>Hounsfield units on CT were negatively associated with increased hepatic vacuolation, while ultrasound and gross evaluation of the liver were not reliable. Beta-hydroxybutyric-acid (BHBA) concentrations were significantly associated with hepatic lipidosis. Metabolomics and lipidomics data found BHBA and succinic acid to be potential biomarkers for diagnosing hepatic lipidosis in bearded dragons. Succinic acid concentrations were significantly lower in the gemfibrozil treatment group. There was a tendency for improvement in the biomarkers and reduced hepatic fat in bearded dragons with hepatic lipidosis when treated with gemfibrozil, though the improvement was not statistically significant.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Conclusions<\/jats:title><jats:p>These findings provide information on the antemortem assessment of hepatic lipidosis in bearded dragons and paves the way for further research in diagnosis and treatment of this disease.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0274060","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T18:36:05Z","timestamp":1675449365000},"page":"e0274060","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of plasma metabolites and diagnostic imaging findings with hepatic lipidosis in bearded dragons (Pogona vitticeps) and effects of gemfibrozil therapy"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4552","authenticated-orcid":true,"given":"Trinita K.","family":"Barboza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-6145","authenticated-orcid":true,"given":"Leonardo","family":"Susta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"zur Linden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gardhouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3612-5548","authenticated-orcid":true,"given":"Hugues","family":"Beaufr\u00e8re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"pone.0274060.ref001","article-title":"Prevalence and risk factors of hepatic lipid changes in bearded dragons (Pogona vitticeps).","author":"T Barboza","year":"2022","journal-title":"Vet Pathol"},{"key":"pone.0274060.ref002","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/B978-0-323-48253-0.00084-2","volume-title":"Mader\u2019s reptile and amphibian medicine and surgery","author":"T Boyer","year":"2019","edition":"3"},{"key":"pone.0274060.ref003","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1053\/ax.2000.7136","article-title":"Reptile hepatic lipidosis","volume":"9","author":"S Divers","year":"2000","journal-title":"Semin Avian and Exot Pet Med"},{"key":"pone.0274060.ref004","first-page":"219","volume-title":"Tratado de animais selvagens","author":"Dutra G. Testudines","year":"2014"},{"key":"pone.0274060.ref005","first-page":"633","article-title":"Diagnostic value of hepatic enzymes, triglycerides and serum proteins for the detection of hepatic lipidosis in chelonoidis carbonaria in captivity","volume":"8","author":"G. Durta","year":"2014","journal-title":"J Life Sci"},{"key":"pone.0274060.ref006","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0305-0491(94)90176-7","article-title":"Regulation of lipid metabolism in poikilothermic vertebrates","volume":"107","author":"M. Sheridan","year":"1994","journal-title":"Comp Biochem Physiol B"},{"key":"pone.0274060.ref007","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/B0-72-169327-X\/50060-2","volume-title":"Reptile medicine and surgery","author":"S. Hernandez-Divers","year":"2006","edition":"2"},{"key":"pone.0274060.ref008","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/9780470698877.ch13","volume-title":"Medicine and surgery of tortoises and turtles","author":"S. McArthur","year":"2004"},{"key":"pone.0274060.ref009","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.cvex.2006.05.013","article-title":"Hepatic lipidosis in a black-headed python (Aspidites melanocephalus)","volume":"9","author":"M. Simpson","year":"2006","journal-title":"Vet Clin North Am Exot Anim Pract"},{"key":"pone.0274060.ref010","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/brv.12288","article-title":"The physiology of lipid storage and use in reptiles","volume":"92","author":"E. Price","year":"2017","journal-title":"Biol Rev Camb Philos Soc"},{"key":"pone.0274060.ref011","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1517\/14656566.4.5.611","article-title":"Current best treatment for non-alcoholic fatty liver disease","volume":"4","author":"P. Angulo","year":"2003","journal-title":"Expert Opin Pharmacother"},{"key":"pone.0274060.ref012","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00535-013-0758-5","article-title":"Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease","volume":"48","author":"Y Kawano","year":"2013","journal-title":"J Gastroenterol"},{"key":"pone.0274060.ref013","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5818\/1529-9651-20.2.54","article-title":"Gastrointestinal disturbances in a bearded dragon (Pogona vitticeps).","volume":"20","author":"D Perpinan","year":"2010","journal-title":"J Herpetol Med Surg"},{"key":"pone.0274060.ref014","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.jacl.2018.03.089","article-title":"Dyslipidemia is associated with pediatric nonalcoholic fatty liver disease","volume":"12","author":"S Dowla","year":"2018","journal-title":"J Clin Lipidol"},{"key":"pone.0274060.ref015","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00125-005-0070-x","article-title":"Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects","volume":"49","author":"H Holt","year":"2006","journal-title":"Diabetologia"},{"key":"pone.0274060.ref016","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1194\/jlr.P055640","article-title":"Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis","volume":"56","author":"R Loomba","year":"2015","journal-title":"J Lipid Res"},{"key":"pone.0274060.ref017","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.bbrc.2018.05.078","article-title":"Non-alcoholic fatty liver disease: Insights from sphingolipidomics","volume":"504","author":"D Montefusco","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"pone.0274060.ref018","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/hep.23229","article-title":"The plasma lipidomic signature of nonalcoholic steatohepatitis","volume":"50","author":"P Puri","year":"2009","journal-title":"Hepatology"},{"key":"pone.0274060.ref019","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1007\/s00125-013-2981-2","article-title":"Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids","volume":"56","author":"M Ore\u0161i\u010d","year":"2013","journal-title":"Diabetologia"},{"key":"pone.0274060.ref020","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1194\/jlr.P056002","article-title":"Biomarkers of NAFLD progression: a lipidomics approach to an epidemic","volume":"56","author":"D Gordon","year":"2015","journal-title":"J Lipid Res"},{"key":"pone.0274060.ref021","first-page":"158","article-title":"Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases","volume":"9","author":"A Safaei","year":"2016","journal-title":"Gastroenterol Hepatol Bed Bench"},{"key":"pone.0274060.ref022","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2174\/1874467208666150817111419","article-title":"The hepatic lipidome: a gateway to understanding the pathogenesis of alcohol-induced fatty liver","volume":"10","author":"R Clugstion","year":"2017","journal-title":"Curr Mol Pharmacol"},{"key":"pone.0274060.ref023","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1177\/1040638720948505","article-title":"Metabolomics in the study of spontaneous animal diseases","volume":"32","author":"H Tran","year":"2020","journal-title":"J Vet Diagn Invest"},{"key":"pone.0274060.ref024","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/vcp.12895","article-title":"Lipoprotein characterization in quaker parrots (Myiopsitta monachus) using gel-permeation high-performance liquid chromatography","volume":"49","author":"H Beaufrere","year":"2020","journal-title":"Vet Clin Pathol"},{"key":"pone.0274060.ref025","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/0305-0491(72)90128-9","article-title":"Fatty acid distribution of lipids from carcass, liver and fat bodies of the lizard Cnemidophorus tigris, prior to hibernation","volume":"41B","author":"B Brian","year":"1972","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"pone.0274060.ref026","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF00714571","article-title":"Dietary fats, selected body temperature and tissue fatty acid composition of agamid lizards (Amphibolurus nuchalis).","volume":"164","author":"F Geiser","year":"1994","journal-title":"J Comp Physiol B"},{"key":"pone.0274060.ref027","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.cbpb.2005.07.013","article-title":"Effects of ambient temperature on lipid and fatty acid composition in the oviparous lizards, Phrynocephalus przewalskii","volume":"142","author":"J Shen","year":"2005","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"pone.0274060.ref028","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.2460\/javma.230.7.1049","article-title":"Coelioscopic-assisted prefemoral oophorectomy in chelonians","volume":"230","author":"C Innis","year":"2007","journal-title":"J Am Vet Med Assoc"},{"key":"pone.0274060.ref029","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5818\/1529-9651-22.3.117","article-title":"Husbandry, diseases, and veterinary care of the bearded dragon (Pogona vitticeps).","volume":"22","author":"P Raiti","year":"2012","journal-title":"J Herpetol Med Surg"},{"key":"pone.0274060.ref030","article-title":"Morphological features of hepatic lipid changes in bearded dragons (Pogona vitticeps), and a proposed grading system","author":"T Barboza","year":"2022","journal-title":"Vet Pathol"},{"key":"pone.0274060.ref031","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of LIver Diseases","volume":"67","author":"N Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"pone.0274060.ref032","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cvsm.2009.02.006","article-title":"Liver biopsy techniques","volume":"39","author":"J Rothuizen","year":"2009","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"pone.0274060.ref033","first-page":"189","article-title":"Magnetic resonance imaging and computerized tomography of a gravid leopard tortoise (Geochelone pardalis pardalis) with metabolic bone disease","volume":"28","author":"P Raiti","year":"1997","journal-title":"J Zoo Wildl Med"},{"key":"pone.0274060.ref034","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1638\/2014-0178R2.1","article-title":"Use of computed tomography for investigation of hepatic lipidosis in captive Chelonoidis Carbonaria (SPIX, 1824).","volume":"46","author":"A Marchiori","year":"2015","journal-title":"J Zoo Wildl Med"},{"key":"pone.0274060.ref035","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1148\/130.2.511","article-title":"The relation of liver fat to computed tomography numbers: a preliminary experimental study in rabbits","volume":"130","author":"J Ducommun","year":"1979","journal-title":"Radiol"},{"key":"pone.0274060.ref036","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/01.rct.0000193818.31749.84","article-title":"Computed Tomography Features of Nonalcoholic Steatohepatitis With Histopathologic Correlation","volume":"30","author":"M Oliva","year":"2006","journal-title":"J Comput Assist Tomogr"},{"key":"pone.0274060.ref037","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cvsm.2016.11.006","article-title":"Diagnostic imaging of the hepatobiliary system: an update","volume":"47","author":"A. Marolf","year":"2017","journal-title":"Vet Clin North Am Small Amin Pract"},{"key":"pone.0274060.ref038","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00330-010-1905-5","article-title":"The diagnostic accuracy of US, CT, MRI, and H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis","volume":"21","author":"A Bohte","year":"2011","journal-title":"Eur Radiol"},{"key":"pone.0274060.ref039","doi-asserted-by":"crossref","first-page":"320","DOI":"10.2214\/AJR.07.2123","article-title":"Interobserver and intraobserver variability in the sonographic assessment of fatty liver","volume":"189","author":"S Strauss","year":"2007","journal-title":"AJR Am J Roentgenol"},{"key":"pone.0274060.ref040","doi-asserted-by":"crossref","first-page":"212","DOI":"10.2460\/ajvr.69.2.212","article-title":"Statistical relevance of ultrasonographic criteria in the assessment of diffuse liver disease in dogs and cats","volume":"69","author":"D Feeney","year":"2008","journal-title":"Am J Vet Res"},{"key":"pone.0274060.ref041","unstructured":"Wachsmann S. Ultraschall Untersuchungen bei Bartagamen (Pogona vitticeps) unter Ber\u00fccksichtigung klinischer, r\u00f6ntgenologischer und labor diagnostischer Parameter, electronic, scholarly journal, Dr. Med. Vet. Thesis, University of Veterinary Medicine Hannover. 2010. Available from: https:\/\/elib.tiho-hannover.de\/receive\/etd_mods_00001207"},{"key":"pone.0274060.ref042","doi-asserted-by":"crossref","first-page":"868","DOI":"10.2460\/javma.246.8.868","article-title":"Ultrasonographic anatomy of bearded dragons (Pogona vitticeps).","volume":"246","author":"D Bucy","year":"2015","journal-title":"J Am Vet Med Assoc"},{"key":"pone.0274060.ref043","article-title":"Hepatic lipidosis in reptiles","author":"M. Silvester","year":"2013","journal-title":"South European veterinary conference"},{"key":"pone.0274060.ref044","article-title":"A clinician\u2019s approach to liver disease in tortoises","author":"S. Divers","year":"1997","journal-title":"Proceedings sssociation of reptilian and amphibian veterinarians"},{"key":"pone.0274060.ref045","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3748\/wjg.14.22","article-title":"Role of peroxisome proliferator-activated receptors int he pathogenesis and treatment of nonalcoholic fatty liver disease","volume":"14","author":"E Kallwitz","year":"2008","journal-title":"World J Gastroenterol"},{"key":"pone.0274060.ref046","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/S0140-6736(10)60656-3","article-title":"Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis","volume":"375","author":"M Jun","year":"2010","journal-title":"Lancet"},{"key":"pone.0274060.ref047","author":"M Gurr","year":"2016","edition":"6"},{"key":"pone.0274060.ref048","first-page":"39","article-title":"Mode of action of fibrates in the regulation of triglyceride and HDL-cholesterol metabolism","volume":"42","author":"J Fruchart","year":"2006","journal-title":"Drugs Today (Barc)."},{"key":"pone.0274060.ref049","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biochi.2016.11.009","article-title":"PPARs and nonalcoholic fatty liver disease","volume":"136","author":"K Liss","year":"2017","journal-title":"Biochimie"},{"key":"pone.0274060.ref050","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3184\/175815514X14067215301247","article-title":"The effects of dietary L-carnitine and gemfibrozil on preformance, carcass characteristics, cholesterol and triglycerides in broiler chicks","volume":"7","author":"P Farrokhyan","year":"2014","journal-title":"Avian Biol Res"},{"key":"pone.0274060.ref051","doi-asserted-by":"crossref","first-page":"4731","DOI":"10.1021\/jf990481+","article-title":"Effect of dietary lipid-lowering drugs upon plasma lipids and egg yolk cholesterol levels of laying hens","volume":"47","author":"A Mori","year":"1999","journal-title":"J Agic Food Chem"},{"key":"pone.0274060.ref052","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1161\/01.CIR.85.1.37","article-title":"Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment","volume":"85","author":"V Manninen","year":"1992","journal-title":"Circulation"},{"key":"pone.0274060.ref053","first-page":"40","article-title":"Regulation of vitellogenesis in reptiles","volume":"38","author":"S Ho","year":"1982","journal-title":"Herpetologica"},{"key":"pone.0274060.ref054","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"F Faul","year":"2007","journal-title":"Behav Res Methods"},{"key":"pone.0274060.ref055","first-page":"42","article-title":"A preliminary feeding study in bearded dragon lizards, Pogona vitticeps","volume":"9","author":"K Douglas","year":"1999","journal-title":"J Herpetol Med Surg"},{"key":"pone.0274060.ref056","first-page":"205","article-title":"Husbandry and veterinary aspects of the bearded dragon (Pogona spp.) in Australia.","volume":"12","author":"M Cannon","year":"2003","journal-title":"J Exot Pet Med"},{"key":"pone.0274060.ref057","first-page":"12","article-title":"General husbandry and captive propagation of bearded dragons, Pogona vitticeps","volume":"9","author":"S. Stahl","year":"1999","journal-title":"J Herpetol Med Surg"},{"key":"pone.0274060.ref058","unstructured":"Attard L. The development and evaluation of a gut-loading diet for feeder crickets formulated to provide a balanced nutrient source for insectivorous amphibians and reptiles, electronic, scholarly journal. M.Sc. Thesis, The University of Guelph. 2013. Available from: http:\/\/hdl.handle.net\/10214\/6653"},{"key":"pone.0274060.ref059","unstructured":"Coslik A, Ward A, McClements R. Gut loading as a method to effectively supplement crickets with calcium and vitamin A. Proceedings of the 8th conference on Zoo and Wildlife Nutriition, AZA Nutrition Advisory Group. 2009. Available from: https:\/\/nagonline.net\/wp-content\/uploads\/2014\/04\/33_CoslikCricketVitA.pdf"},{"key":"pone.0274060.ref060","first-page":"26","article-title":"Dietary manipulation of the calcium concentration of feed crickets.","volume":"20","author":"M Allen","year":"1989","journal-title":"J Zoo Wildl Med"},{"key":"pone.0274060.ref061","unstructured":"AB Sciex Pte. Ltd. Analyst 1.6.3 software release notes. 2015 [Cited 2022 Jan 30]. Available from: https:\/\/download.sciex.com\/Analyst_1.6.3_RelNotes.pdf"},{"key":"pone.0274060.ref062","first-page":"31","article-title":"LipoSEARCH\u00ae; Analytical GP-HPLC method for lipoprotein profiling and its applications.","volume":"13","author":"G Toshima","year":"2013","journal-title":"J Biol Macromol"},{"key":"pone.0274060.ref063","doi-asserted-by":"crossref","first-page":"265","DOI":"10.5650\/jos.ess16020","article-title":"Recent advances in analytical methods on lipoprotein subclasses: calculation of particle numbers from lipid levels by gel permeation HPLC using \u201cspherical particle model.\u201d","volume":"65","author":"M Okazaki","year":"2016","journal-title":"J Oleo Sci"},{"key":"pone.0274060.ref064","doi-asserted-by":"crossref","first-page":"855.e10","DOI":"10.1016\/j.vaa.2020.07.026","article-title":"Pharmacodynamics and pharmacokinetics of intramuscular alfaxalone in central bearded dragons (Pogona vitticeps): effect of injection site","volume":"47","author":"S Shippy","year":"2020","journal-title":"Vet Anaesth Analg"},{"key":"pone.0274060.ref065","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.vaa.2018.12.002","article-title":"Pharmacokinetics of subcutaneously administered hydromorphone in bearded dragons (Pogona vitticeps) and red-eared slider turtles (Trachemys scripta elegans).","volume":"46","author":"S Hawkins","year":"2019","journal-title":"Vet Anaesth Analg"},{"key":"pone.0274060.ref066","author":"WS Rasband","year":"1997","journal-title":"ImageJ. U.S. National Institutes of Health"},{"key":"pone.0274060.ref067","first-page":"16","article-title":"A review of reptile diagnostic coelioscopy","volume":"15","author":"S Hernandez-Divers","year":"2005","journal-title":"J Herp Med Surg"},{"key":"pone.0274060.ref068","author":"The R Core Team","year":"2020"},{"key":"pone.0274060.ref069","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/B978-0-323-48253-0.00126-4","volume-title":"Mader\u2019s Reptile and Amphibian Medicine and Surgery","author":"J. Mayer","year":"2019","edition":"3"},{"key":"pone.0274060.ref070","unstructured":"National Center for Biotechnology Information. PubChem Compound Summary for CID 3463, Gemfibrozil. 2004 [Cited 2022 Jan 30]. In: PubChem [Internet]. Available from: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Gemfibrozil."},{"key":"pone.0274060.ref071","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3390\/metabo9070143","article-title":"Statistical workflow for feature selection in human metabolomics data.","volume":"9","author":"J Antonelli","year":"2019","journal-title":"Metabolites"},{"key":"pone.0274060.ref072","doi-asserted-by":"crossref","first-page":"W486","DOI":"10.1093\/nar\/gky310","article-title":"MetaboAnalyst 4.0: towards more transparent and integrative metabolomics analysis","volume":"46","author":"J Chong","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pone.0274060.ref073","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.2460\/ajvr.73.7.1002","article-title":"Influence of dietary supplementation with L-carnitine on metabolic rate, fatty acid oxidation, body condition, and weight loss in overweight cats","volume":"73","author":"S Center","year":"2012","journal-title":"Am J Vet Res"},{"key":"pone.0274060.ref074","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/MPG.0000000000002875","article-title":"Lipidomics in non-alcoholic fatty liver disease: exploring serum lipids as biomarkers for pediatric NAFLD","volume":"71","author":"L Draijer","year":"2020","journal-title":"J Pediatr Gastroentrol Nutrition"},{"key":"pone.0274060.ref075","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1194\/jlr.M086405","article-title":"Fatty liver disrupts glycerol metabolism in gluconeogenic and lipogenic pathways in humans","volume":"59","author":"E Jin","year":"2018","journal-title":"J Lipids Res"},{"key":"pone.0274060.ref076","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1111\/apt.16066","article-title":"Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease","volume":"52","author":"Y Jung","year":"2020","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0274060.ref077","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S2221-1691(13)60177-X","article-title":"Comparison of lipid profile in different grades of non-alcoholic fatty liver disease diagnosed on ultrasound","volume":"3","author":"D Mahaling","year":"2013","journal-title":"Asian Pac J Trop Biomed"},{"key":"pone.0274060.ref078","article-title":"Decreases in circulating concentrations of long-chain acylcarnitines and free fatty acids during the glucose tolerance test represent tissue-specific insulin sensitivity.","author":"E Makarova","year":"2019","journal-title":"Front Endocrinol"},{"key":"pone.0274060.ref079","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.3748\/wjg.v25.i24.3009","article-title":"Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease","volume":"25","author":"J Mato","year":"2019","journal-title":"World J Gastroenterol"},{"key":"pone.0274060.ref080","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12328-012-0315-4","article-title":"Nonalcoholic fatty liver disease: from lipid profile to treatment","volume":"5","author":"K Milura","year":"2012","journal-title":"Clin J Gastroenterol"},{"key":"pone.0274060.ref081","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jbior.2018.11.004","article-title":"non-alcoholic fatty liver disease: Focus on ceramide","volume":"70","author":"Nikolova-Karakashian M. Alcoholic","year":"2018","journal-title":"Adv Biol Regul"},{"key":"pone.0274060.ref082","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1111\/hepr.13528","article-title":"Metabolomic\/ lipidomic-based analysis of plasma to diagnose hepatocellular ballooning in patients with non-alcoholic fatty liver disease: A multicenter study","volume":"50","author":"Y Ogawa","year":"2020","journal-title":"Hepatol Res"},{"key":"pone.0274060.ref083","doi-asserted-by":"crossref","first-page":"108519","DOI":"10.1016\/j.jnutbio.2020.108519","article-title":"Liver lipidome signature and metabolic pathways in nonalcoholic fatty liver disease induced by a high sugar diet","volume":"87","author":"D Oliveira","year":"2021","journal-title":"J Nutr Biochem"},{"key":"pone.0274060.ref084","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1007\/s00394-019-02068-4","article-title":"Does L-carnitine supplementation affect serum levels of enzyme mainly produced by liver? A systematic review and meta-analysis of randomized controlled clinical trials","volume":"59","author":"F Pirmadah","year":"2020","journal-title":"Eur J Nutr"},{"key":"pone.0274060.ref085","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12917-020-2257-2","article-title":"Development, diagnosis and therapy of ketosis in non-gravid and non-lactating guinea pigs","volume":"16","author":"N Schmid","year":"2020","journal-title":"BMC Vet Res"},{"key":"pone.0274060.ref086","first-page":"28","article-title":"Significance of cholesterol assays in the investigation of hepatic lipidosis and atherosclerosis in psittacine birds","volume":"7","author":"M. Stanford","year":"2005","journal-title":"Exotic DVM"},{"key":"pone.0274060.ref087","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/1746-6148-10-112","article-title":"Evaluation of liver parenchyma and perfusion using dynamic contrast-enhanced computed tomography and contrast-enhanced ultrasonography in captive green iguanas (Iguana iguana) under general anesthesia","volume":"10","author":"G Nardini","year":"2014","journal-title":"BMC Vet Res"},{"key":"pone.0274060.ref088","doi-asserted-by":"crossref","first-page":"674","DOI":"10.17221\/73\/2017-VETMED","article-title":"Contrast-enhanced computed tomography of the liver, gall bladder and urogenital tract in female red-eared terrapins (Trachemys scripta elegans).","volume":"62","author":"V Sochorcova","year":"2017","journal-title":"Veterinarni Medicina"},{"key":"pone.0274060.ref089","first-page":"1220","volume-title":"Veterinary computed tomography.","author":"M Gumpenberger","year":"2011"},{"key":"pone.0274060.ref090","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1638\/2012-0123R1.1","article-title":"Quantitative computed tomography of the liver in juvenile green sea turtles (Chelonia mydas).","volume":"44","author":"M Bonelli","year":"2013","journal-title":"J Zoo Wildl Med"},{"key":"pone.0274060.ref091","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/vru.12827","article-title":"Hepatic CT attenuation differs in three sepcies of freshwater turtles and hepatic Hounsfield units increase with folliculogenesis in wild Blanding\u2019s turtles (Emydoidea blandingii).","volume":"61","author":"E King","year":"2020","journal-title":"Vet Radiol Ultrasound"},{"key":"pone.0274060.ref092","first-page":"539","article-title":"Tomograhic attenuation of the hepatic parenchyma of adult free-ranging and captive boas (Boa Constrictor).","volume":"51","author":"J de Souza","year":"2020","journal-title":"J Zoo Wildl Med"},{"key":"pone.0274060.ref093","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/vru.12820","article-title":"Ultrasonographic appearance of the coelomic cavity organs in healthy veiled chameleons (Chamaeleo calyptratus) and panther chameleons (Furcifer pardalis).","volume":"61","author":"A Melero","year":"2019","journal-title":"Vet Radiol Ultrasound"},{"key":"pone.0274060.ref094","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/B978-0-323-48253-0.00058-1","volume-title":"Mader\u2019s reptile and amphibian medicine and surgery","author":"C Hochleithner","year":"2019","edition":"3"},{"key":"pone.0274060.ref095","doi-asserted-by":"crossref","first-page":"55","DOI":"10.4103\/0973-6042.76960","article-title":"Ultrasound: basic understanding and learning the language.","volume":"4","author":"B Ihnatsenka","year":"2010","journal-title":"Int J Shoulder Surg"},{"key":"pone.0274060.ref096","first-page":"210","volume-title":"BSAVA manual of reptiles","author":"S McArthur","year":"2019"},{"key":"pone.0274060.ref097","first-page":"124","article-title":"Plasma bile acids in reptiles","author":"Z Knotek","year":"2009","journal-title":"Proceedings of the association of reptilian and amphibian veterinarians."},{"key":"pone.0274060.ref098","article-title":"Alternative treatment options for managing hepatic lipidosis in an atlantic ridley sea turtle (Lepidochelys kempii).","author":"R Ahlstrom","year":"2012","journal-title":"International association for aquatic animal medicine"},{"key":"pone.0274060.ref099","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.biopha.2009.06.003","article-title":"Effect of atorvastatin and diet on non-alcoholic fatty liver disease activity scroe in hyperlipidemic chickens","volume":"64","author":"A Martin-Castillo","year":"2010","journal-title":"Biomed Pharmacother"},{"key":"pone.0274060.ref100","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1053\/j.jepm.2013.05.006","article-title":"Clinical update on diagnosis and management of disorders of the digestive system of reptiles","volume":"22","author":"C. Mans","year":"2013","journal-title":"J Exot Pet Med"},{"key":"pone.0274060.ref101","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1136\/vr.163.17.510","article-title":"Fasting and postprandial serum bile acid concentrations in 10 healthy female red-eared terrapins (Trachemys scripta elegans).","volume":"163","author":"Z Knotkova","year":"2008","journal-title":"Vet Rec"},{"key":"pone.0274060.ref102","first-page":"129","article-title":"Preliminary evaluation of pre- and post- prandial 3a-hydroxy-bile-acids in the green iguana (Iguana iguana).","volume":"16","author":"M McBride","year":"2006","journal-title":"J Herp Med Surg"},{"key":"pone.0274060.ref103","article-title":"Role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease","author":"M Masarone","year":"2018","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0274060.ref104","doi-asserted-by":"crossref","first-page":"e127737","DOI":"10.1172\/jci.insight.127737","article-title":"Impaired ketogenesis and increased acetyl-CoA oxidation promote hyperglycemia in human fatty liver","volume":"4","author":"J Fletcher","year":"2019","journal-title":"JCI Insight"},{"key":"pone.0274060.ref105","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biocel.2017.12.019","article-title":"Mitochondria in non-alcoholic fatty liver disease","volume":"95","author":"I Simoes","year":"2018","journal-title":"Int J Bioch Cell Bio"},{"key":"pone.0274060.ref106","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.cmet.2011.11.004","article-title":"Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease","volume":"14","author":"N Sunny","year":"2011","journal-title":"Cell Metab"},{"key":"pone.0274060.ref107","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.3748\/wjg.v23.i15.2685","article-title":"Changes in human hepatic metabolism in steatosis and cirrhosis","volume":"23","author":"Z Schofield","year":"2017","journal-title":"World J Gastroenterol"},{"key":"pone.0274060.ref108","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/j.1742-4658.2010.07947.x","article-title":"Fatty acid omega\u2010oxidation as a rescue pathway for fatty acid oxidation disorders in humans.","volume":"278","author":"R Wanders","year":"2011","journal-title":"FEBS J."},{"key":"pone.0274060.ref109","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.bbamcr.2016.01.023","article-title":"Carnitine transport and fatty acid oxidation","volume":"1863","author":"N Long","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"pone.0274060.ref110","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.cvsm.2016.11.014","article-title":"Feline hepatic lipidosis","volume":"47","author":"C Valtolina","year":"2017","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"pone.0274060.ref111","doi-asserted-by":"crossref","first-page":"46658","DOI":"10.1038\/srep46658","article-title":"Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients","volume":"7","author":"F Chiappini","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0274060.ref112","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1242\/jeb.007286","article-title":"Differences in membrane acyl phospholipid composition between an endothermic mammal and an ectothermic reptile are not limited to any phospholipid class","volume":"210","author":"T Mitchell","year":"2007","journal-title":"J Exp Biol"},{"key":"pone.0274060.ref113","doi-asserted-by":"crossref","first-page":"47402","DOI":"10.1074\/jbc.M404027200","article-title":"Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins","volume":"279","author":"R Jacobs","year":"2004","journal-title":"J Biol Chem"},{"key":"pone.0274060.ref114","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1093\/jn\/132.1.68","article-title":"Choline deficiency-induced liver damage is reversible in Pemt(-\/-) mice","volume":"132","author":"K Waite","year":"2002","journal-title":"J Nutr"},{"key":"pone.0274060.ref115","doi-asserted-by":"crossref","first-page":"22403","DOI":"10.1074\/jbc.M110.108514","article-title":"Impaired de novo choline synthesis explains why phosphatidylethanolamine N-methyltransferase-deficient mice are protected from diet-induced obesity","volume":"285","author":"R Jacobs","year":"2010","journal-title":"J Biol Chem"},{"key":"pone.0274060.ref116","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.cell.2011.09.045","article-title":"A conserved SREBP 1\/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans","volume":"147","author":"A Walker","year":"2011","journal-title":"Cell"},{"key":"pone.0274060.ref117","first-page":"888","article-title":"Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function","volume":"1841","author":"N Hollie","year":"2014","journal-title":"Biochem Biophys Acta"},{"key":"pone.0274060.ref118","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00216-018-1506-8","article-title":"Mapping the triglyceride distribution in NAFLD human liver by MALDI imaging mass spectrometry reveals molecular differences in micro and macro steatosis","volume":"411","author":"H Alamri","year":"2019","journal-title":"Anal Bioanal Chem"},{"key":"pone.0274060.ref119","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1194\/jlr.R066357","article-title":"Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis","volume":"57","author":"P Hirsova","year":"2016","journal-title":"J Lipid Res"},{"key":"pone.0274060.ref120","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.plipres.2012.10.004","article-title":"Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease","volume":"52","author":"A Leamy","year":"2013","journal-title":"Prog Lipid Res"},{"key":"pone.0274060.ref121","first-page":"R857","article-title":"Control of adipose tissue lipolysis in ectotherm vertebrates","volume":"263","author":"R Migliorini","year":"1992","journal-title":"Am J Physiol"},{"key":"pone.0274060.ref122","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: lessons from sphingolipids","volume":"9","author":"Y Hannun","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0274060.ref123","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1210\/er.2007-0025","article-title":"Sphingolipids, insulin resistance, and metabolic disease: New insights from in vivo manipulation of sphingolipid metabolism","volume":"29","author":"W Holland","year":"2008","journal-title":"Endocr Rev"},{"key":"pone.0274060.ref124","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jhep.2010.05.037","article-title":"Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity","volume":"54","author":"P Simonen","year":"2011","journal-title":"J Hepatol"},{"key":"pone.0274060.ref125","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s00535-006-1883-1","article-title":"Cholesterol-fed rabbit as a unique model of nonalcoholic, nonobese, non-insulin-resistant fatty liver disease with characteristic fibrosis","volume":"41","author":"M Kainuma","year":"2006","journal-title":"J Gastroenterol"},{"key":"pone.0274060.ref126","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/hep.21874","article-title":"Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet.","volume":"46","author":"N Matsuzawa","year":"2007","journal-title":"Hepatol"},{"key":"pone.0274060.ref127","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1177\/0300985818800025","article-title":"Lipid-related lesions in quaker parrots (Myiopsitta monachus).","volume":"56","author":"H Beaufrere","year":"2019","journal-title":"Vet Pathol"},{"key":"pone.0274060.ref128","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/B978-0-323-48253-0.00067-2","volume-title":"Mader\u2019s reptile and amphibian medicine and surgery","author":"S Divers","year":"2019","edition":"3"},{"key":"pone.0274060.ref129","unstructured":"Gelens T. Histological and immunohistochemical characterizatino of feling hepatic lipidosis, electronic, scholarly journal. M.Sc. Thesis, Utrecht University. 2013. Available from: http:\/\/dspace.library.uu.nl\/handle\/1874\/292946"},{"key":"pone.0274060.ref130","unstructured":"Valtolina C. Pathophysiologic Aspects of Feliine Hepatic Lipidosis, electronic, scholarly journal. PhD. Thesis, Utrecht Univeristy. 2019. Available from: https:\/\/dspace.library.uu.nl\/bitstream\/1874\/379615\/1\/pathophysiologicaspectsoffelinehepaticlipidosischiaravaltolina.pdf"},{"key":"pone.0274060.ref131","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.cvsm.2004.10.002","article-title":"Feline hepatic lipidosis","volume":"35","author":"S. Center","year":"2005","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"pone.0274060.ref132","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.tvjl.2011.01.010","article-title":"A retrospecitve study of serum beta-hydroxybutyric acid in 215 ill cats: Clinical signs, laboratory findings and diagnoses","volume":"191","author":"I Aroch","year":"2012","journal-title":"Vet J"},{"key":"pone.0274060.ref133","doi-asserted-by":"crossref","first-page":"17854","DOI":"10.1038\/s41598-020-73706-9","article-title":"MicroRNA dynamics during hibernation of the Australian central bearded dragon (Pogona vitticeps)","volume":"10","author":"A Capraro","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0274060.ref134","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cbpc.2015.09.011","article-title":"Gemfibrozil disrupts the metabolism of circulating lipids in bobwhite quails","volume":"179","author":"S Bussiere-Cote","year":"2016","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"key":"pone.0274060.ref135","unstructured":"Cayman Chemicals. Gemfibrozil MSDS. 2019. Available from: https:\/\/www.caymanchem.com\/msdss\/14835m.pdf"},{"key":"pone.0274060.ref136","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1242\/jeb.01553","article-title":"Field metabolic rate and body size","volume":"208","author":"K. Nagy","year":"2005","journal-title":"J Exp Biol"},{"key":"pone.0274060.ref137","unstructured":"Barboza T. Hepatic lipidosis in the bearded dragon (Pogona vittieps): diagnostic and therapeutic investigations, electronic, scholarly journal. DVSc. Thesis, The University of Guelph. 2021. Available from: https:\/\/hdl.handle.net\/10214\/26230"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0274060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T05:51:24Z","timestamp":1701841884000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0274060"}},"subtitle":[],"editor":[{"given":"Nobuyuki","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,2,3]]},"references-count":137,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0274060","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,3]]}}}