{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T12:21:24Z","timestamp":1767183684080,"version":"3.37.3"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8J0881"],"award-info":[{"award-number":["CMRPG8J0881"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8J0882"],"award-info":[{"award-number":["CMRPG8J0882"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>A maternal high-fat diet (HFD) can impact the offspring\u2019s development of liver steatosis, with fetal development in utero being a crucial period. Therefore, this study investigated the mechanism and whether butyrate can rescue liver injury caused by maternal HFD in the fetus. Pregnant female Sprague Dawley rats were randomly divided into two groups, prenatal HFD (58% fat) exposure or normal control diet (4.5% fat). The HFD group was fed an HFD 7 weeks before mating and during gestation until sacrifice at gestation 21 days. After confirmation of mating, the other HFD group was supplemented with sodium butyrate (HFSB). The results showed that maternal liver histology showed lipid accumulation with steatosis and shortened ileum villi in HFD, which was ameliorated in the HFSB group (P&lt;0.05). There was increased fetal liver and ileum TUNEL staining and IL-6 expression with increased fetal liver TNF-\u03b1 and malondialdehyde expression in the HFD group (P&lt;0.05), which decreased in the HFSB group (P&lt;0.05). The fetal liver expression of phospho-AKT\/AKT and GPX1 decreased in the HFD group but increased in the HFSB group (P&lt;0.05). In conclusion that oxidative stress with inflammation and apoptosis plays a vital role after maternal HFD in the fetus liver that can be ameliorated with butyrate supplementation.<\/jats:p>","DOI":"10.1371\/journal.pone.0270657","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T17:36:19Z","timestamp":1657128979000},"page":"e0270657","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Butyrate ameliorates maternal high-fat diet-induced fetal liver cellular apoptosis"],"prefix":"10.1371","volume":"17","author":[{"given":"Yu-Jyun","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo-Shu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Jen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Hsien","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-3495","authenticated-orcid":true,"given":"Mao-Meng","family":"Tiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"issue":"2","key":"pone.0270657.ref001","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1017\/S2040174414000580","article-title":"Evolution of DOHaD: the impact of environmental health sciences","volume":"6","author":"AC Haugen","year":"2015","journal-title":"J Dev Orig Health Dis"},{"issue":"1","key":"pone.0270657.ref002","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1017\/S2040174415001269","article-title":"Fetal programming of overweight through the microbiome: boys are disproportionately affected","volume":"7","author":"AL Kozyrskyj","year":"2016","journal-title":"J Dev Orig Health Dis"},{"issue":"6","key":"pone.0270657.ref003","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.2337\/dc08-2077","article-title":"Fetuses of obese mothers develop insulin resistance in utero","volume":"32","author":"PM Catalano","year":"2009","journal-title":"Diabetes care"},{"issue":"1\u20132","key":"pone.0270657.ref004","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/pr.2013.193","article-title":"Developmental origins of nonalcoholic fatty liver disease","volume":"75","author":"DE Brumbaugh","year":"2014","journal-title":"Pediatr Res"},{"issue":"4","key":"pone.0270657.ref005","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.clnu.2008.05.005","article-title":"Deleterious effects of high-fat diet on perinatal and postweaning periods in adult rat offspring","volume":"27","author":"LB Parente","year":"2008","journal-title":"Clin Nutr"},{"issue":"8","key":"pone.0270657.ref006","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.3390\/ijerph17082780","article-title":"Maternal Resveratrol Treatment Re-Programs and Maternal High-Fat Diet-Induced Retroperitoneal Adiposity in Male Offspring","volume":"17","author":"TA Tsai","year":"2020","journal-title":"International journal of environmental research and public health"},{"issue":"1","key":"pone.0270657.ref007","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s12944-018-0824-3","article-title":"Resveratrol ameliorates maternal and post-weaning high-fat diet-induced nonalcoholic fatty liver disease via renin-angiotensin system","volume":"17","author":"MM Tiao","year":"2018","journal-title":"Lipids in health and disease"},{"issue":"11","key":"pone.0270657.ref008","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1177\/153537020623101106","article-title":"Gut responses to enteral nutrition in preterm infants and animals","volume":"231","author":"PT Sangild","year":"2006","journal-title":"Exp Biol Med (Maywood)"},{"key":"pone.0270657.ref009","doi-asserted-by":"crossref","first-page":"D299","DOI":"10.2741\/klurfeld","article-title":"Nutritional regulation of gastrointestinal growth","volume":"4","author":"DM Klurfeld","year":"1999","journal-title":"Frontiers in bioscience: a journal and virtual library"},{"issue":"12","key":"pone.0270657.ref010","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s12276-018-0183-1","article-title":"Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression","volume":"50","author":"D Zhou","year":"2018","journal-title":"Experimental & molecular medicine"},{"issue":"1","key":"pone.0270657.ref011","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3748\/wjg.v23.i1.60","article-title":"Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier","volume":"23","author":"D Zhou","year":"2017","journal-title":"World journal of gastroenterology"},{"issue":"7","key":"pone.0270657.ref012","doi-asserted-by":"crossref","first-page":"e68626","DOI":"10.1371\/journal.pone.0068626","article-title":"Effects of sodium butyrate and its synthetic amide derivative on liver inflammation and glucose tolerance in an animal model of steatosis induced by high fat diet","volume":"8","author":"G Mattace Raso","year":"2013","journal-title":"PloS one"},{"issue":"2","key":"pone.0270657.ref013","doi-asserted-by":"crossref","first-page":"e12785","DOI":"10.1111\/hel.12785","article-title":"Effects of sodium butyrate supplementation on inflammation, gut microbiota, and short-chain fatty acids in Helicobacter pylori-infected mice","volume":"26","author":"Y Huang","year":"2021","journal-title":"Helicobacter"},{"issue":"1","key":"pone.0270657.ref014","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1096\/fj.201900927RR","article-title":"Butyrate prevents valproate-induced liver injury: In vitro and in vivo evidence","volume":"34","author":"C Pirozzi","year":"2020","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"1","key":"pone.0270657.ref015","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/s41598-018-36941-9","article-title":"Prominent action of butyrate over beta-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule","volume":"9","author":"S Chriett","year":"2019","journal-title":"Scientific reports"},{"issue":"2","key":"pone.0270657.ref016","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1002\/jcb.27565","article-title":"Sodium butyrate ameliorates lipopolysaccharide-induced cow mammary epithelial cells from oxidative stress damage and apoptosis","volume":"120","author":"L Li","year":"2018","journal-title":"Journal of cellular biochemistry"},{"issue":"29","key":"pone.0270657.ref017","doi-asserted-by":"crossref","first-page":"7633","DOI":"10.1021\/acs.jafc.8b01189","article-title":"Sodium Butyrate Ameliorates High-Fat-Diet-Induced Non-alcoholic Fatty Liver Disease through Peroxisome Proliferator-Activated Receptor alpha-Mediated Activation of beta Oxidation and Suppression of Inflammation","volume":"66","author":"B Sun","year":"2018","journal-title":"Journal of agricultural and food chemistry"},{"issue":"3","key":"pone.0270657.ref018","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3390\/ijms17030369","article-title":"Postnatal High-Fat Diet Increases Liver Steatosis and Apoptosis Threatened by Prenatal Dexamethasone through the Oxidative Effect","volume":"17","author":"YH Huang","year":"2016","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0270657.ref019","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/advances\/nmx009","article-title":"Butyrate: A Double-Edged Sword for Health?","volume":"9","author":"H Liu","year":"2018","journal-title":"Advances in nutrition"},{"issue":"5","key":"pone.0270657.ref020","doi-asserted-by":"crossref","first-page":"e96801","DOI":"10.1371\/journal.pone.0096801","article-title":"IHC Profiler: an open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples","volume":"9","author":"F Varghese","year":"2014","journal-title":"PLoS One"},{"issue":"6","key":"pone.0270657.ref021","doi-asserted-by":"crossref","first-page":"e67791","DOI":"10.1371\/journal.pone.0067791","article-title":"Transgenic increase in N-3\/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice","volume":"8","author":"MJ Heerwagen","year":"2013","journal-title":"PloS one"},{"key":"pone.0270657.ref022","article-title":"The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair","author":"WT Kuo","year":"2021","journal-title":"Gastroenterology"},{"issue":"6","key":"pone.0270657.ref023","first-page":"3521","article-title":"Protective effect of emodin on intestinal epithelial tight junction barrier integrity in rats with sepsis induced by cecal ligation and puncture","volume":"19","author":"Y Li","year":"2020","journal-title":"Experimental and therapeutic medicine"},{"key":"pone.0270657.ref024","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3389\/fendo.2019.00665","article-title":"Inhibiting Ceramide Synthesis Attenuates Hepatic Steatosis and Fibrosis in Rats With Non-alcoholic Fatty Liver Disease","volume":"10","author":"M Jiang","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"2","key":"pone.0270657.ref025","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jss.2004.04.016","article-title":"Akt activation protects rat liver from ischemia\/reperfusion injury","volume":"121","author":"N Harada","year":"2004","journal-title":"J Surg Res"},{"issue":"1\u20132","key":"pone.0270657.ref026","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/pr.2014.169","article-title":"Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk","volume":"77","author":"W Gohir","year":"2015","journal-title":"Pediatr Res"},{"issue":"2","key":"pone.0270657.ref027","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/jn\/nxx027","article-title":"Blueberry Supplementation Influences the Gut Microbiota, Inflammation, and Insulin Resistance in High-Fat-Diet-Fed Rats","volume":"148","author":"S Lee","year":"2018","journal-title":"The Journal of nutrition"},{"issue":"3","key":"pone.0270657.ref028","first-page":"1133","article-title":"Impact of a highfat diet on intestinal stem cells and epithelial barrier function in middleaged female mice","volume":"21","author":"Y Xie","year":"2020","journal-title":"Molecular medicine reports"},{"issue":"5","key":"pone.0270657.ref029","doi-asserted-by":"crossref","first-page":"101066","DOI":"10.1016\/j.psj.2021.101066","article-title":"Effects of multicarbohydrase and butyrate glycerides on productive performance, nutrient digestibility, gut morphology, and ileal microbiota in late-phase laying hens fed corn- or wheat-based diets","volume":"100","author":"H Abbasi Arabshahi","year":"2021","journal-title":"Poultry science"},{"issue":"2","key":"pone.0270657.ref030","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/mbo3.328","article-title":"The programming effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in adult mice","volume":"5","author":"J Zheng","year":"2016","journal-title":"MicrobiologyOpen"},{"issue":"11","key":"pone.0270657.ref031","doi-asserted-by":"crossref","first-page":"3524","DOI":"10.3390\/nu12113524","article-title":"Metabolic Responses to Butyrate Supplementation in LF- and HF-Fed Mice Are Cohort-Dependent and Associated with Changes in Composition and Function of the Gut Microbiota","volume":"12","author":"S Lee","year":"2020","journal-title":"Nutrients"},{"key":"pone.0270657.ref032","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.phrs.2019.01.026","article-title":"Intestinally derived bacterial products stimulate development of nonalcoholic steatohepatitis","volume":"141","author":"W Dornas","year":"2019","journal-title":"Pharmacological research"},{"issue":"3","key":"pone.0270657.ref033","first-page":"188","article-title":"Impact of Propionic Acid on Liver Damage in Rats","volume":"4","author":"S Al-Daihan","year":"2015","journal-title":"International journal of molecular and cellular medicine"},{"issue":"1","key":"pone.0270657.ref034","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1042\/bj2360131","article-title":"Inhibition of oxidative metabolism by propionic acid and its reversal by carnitine in isolated rat hepatocytes","volume":"236","author":"EP Brass","year":"1986","journal-title":"The Biochemical journal"},{"issue":"7","key":"pone.0270657.ref035","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1203\/00006450-197607000-00010","article-title":"Effect of propionic acid on fatty acid oxidation and ureagenesis","volume":"10","author":"AM Glasgow","year":"1976","journal-title":"Pediatr Res"},{"issue":"2","key":"pone.0270657.ref036","first-page":"323","article-title":"Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates","volume":"119","author":"CE McCurdy","year":"2009","journal-title":"The Journal of clinical investigation"},{"issue":"9","key":"pone.0270657.ref037","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/pd.5784","article-title":"Perinatal exposure to maternal obesity: Lasting cardiometabolic impact on offspring","volume":"40","author":"S Kislal","year":"2020","journal-title":"Prenatal diagnosis"},{"issue":"6","key":"pone.0270657.ref038","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1111\/j.1572-0241.2007.01774.x","article-title":"Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis","volume":"103","author":"A Wieckowska","year":"2008","journal-title":"Am J Gastroenterol"},{"key":"pone.0270657.ref039","doi-asserted-by":"crossref","first-page":"4234061","DOI":"10.1155\/2016\/4234061","article-title":"Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases","volume":"2016","author":"S Li","year":"2016","journal-title":"Oxidative medicine and cellular longevity"},{"issue":"36","key":"pone.0270657.ref040","doi-asserted-by":"crossref","first-page":"31263","DOI":"10.1074\/jbc.M111.238147","article-title":"Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium","volume":"286","author":"T Suzuki","year":"2011","journal-title":"The Journal of biological chemistry"},{"issue":"2","key":"pone.0270657.ref041","doi-asserted-by":"crossref","first-page":"e17261","DOI":"10.1371\/journal.pone.0017261","article-title":"Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates","volume":"6","author":"WF Grant","year":"2011","journal-title":"PLoS One"},{"key":"pone.0270657.ref042","doi-asserted-by":"crossref","first-page":"876","DOI":"10.3389\/fphar.2017.00876","article-title":"Psoralea corylifolia L. Attenuates Nonalcoholic Steatohepatitis in Juvenile Mouse","volume":"8","author":"L Zhou","year":"2017","journal-title":"Frontiers in pharmacology"},{"issue":"1","key":"pone.0270657.ref043","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/hep.27804","article-title":"Activation of sphingosine kinase 2 by endoplasmic reticulum stress ameliorates hepatic steatosis and insulin resistance in mice","volume":"62","author":"SY Lee","year":"2015","journal-title":"Hepatology"},{"issue":"3","key":"pone.0270657.ref044","doi-asserted-by":"crossref","first-page":"E39","DOI":"10.1111\/j.1525-1594.2011.01417.x","article-title":"Effect of plasma exchange on hepatocyte oxidative stress, mitochondria function, and apoptosis in patients with acute fatty liver of pregnancy","volume":"36","author":"W Tang","year":"2012","journal-title":"Artif Organs"},{"issue":"5","key":"pone.0270657.ref045","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.cellsig.2012.01.008","article-title":"Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling","volume":"24","author":"PD Ray","year":"2012","journal-title":"Cellular signalling"},{"issue":"5","key":"pone.0270657.ref046","doi-asserted-by":"crossref","first-page":"479","DOI":"10.4314\/ejhs.v26i5.10","article-title":"Plasma Malondialdehyde (MDA): An Indication of Liver Damage in Women with Pre-Eclamsia","volume":"26","author":"AS Atiba","year":"2016","journal-title":"Ethiopian journal of health sciences"},{"issue":"1","key":"pone.0270657.ref047","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jchromb.2005.06.035","article-title":"Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits","volume":"827","author":"R Mateos","year":"2005","journal-title":"Journal of chromatography B, Analytical technologies in the biomedical and life sciences"},{"issue":"2","key":"pone.0270657.ref048","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ajg.2011.04.008","article-title":"Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin","volume":"12","author":"W Samy","year":"2011","journal-title":"Arab journal of gastroenterology: the official publication of the Pan-Arab Association of Gastroenterology"},{"key":"pone.0270657.ref049","doi-asserted-by":"crossref","first-page":"112412","DOI":"10.1016\/j.ecoenv.2021.112412","article-title":"Long term salinity disrupts the hepatic function, intestinal health, and gills antioxidative status in Nile tilapia stressed with hypoxia","volume":"220","author":"MAO Dawood","year":"2021","journal-title":"Ecotoxicology and environmental safety"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270657","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T16:43:07Z","timestamp":1727541787000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270657"}},"subtitle":[],"editor":[{"given":"Catherine","family":"Mounier","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0270657","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2022,7,6]]}}}