{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:09:47Z","timestamp":1785528587460,"version":"3.56.0"},"reference-count":98,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK062965"],"award-info":[{"award-number":["DK062965"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006920","name":"University of Pennsylvania","doi-asserted-by":"publisher","award":["NIH DK19525"],"award-info":[{"award-number":["NIH DK19525"]}],"id":[{"id":"10.13039\/100006920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The prevalence of obesity and non\u2010alcoholic fatty liver disease in children is dramatically increasing at the same time as consumption of foods with a high sugar content. Intake of high fructose corn syrup (HFCS) is a possible aetiology as it is thought to be more lipogenic than glucose.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In a mouse model, HFCS intake during adolescence increased fat mass and hepatic lipid levels in male and female mice. However, only males showed impaired glucose tolerance.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Multiple metabolites including lipids, bile acids, carbohydrates and amino acids were altered in liver in a sex\u2010specific manner at 6\u00a0weeks of age. Some of these changes were also present in adulthood even though HFCS exposure ended at 6\u00a0weeks.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>HFCS significantly altered the gut microbiome, which was associated with changes in key microbial metabolites.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that HFCS intake during adolescence has profound metabolic changes that are linked to changes in the microbiome and these changes are sex\u2010specific.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The rapid increase in obesity, diabetes and fatty liver disease in children over the past 20\u00a0years has been linked to increased consumption of high fructose corn syrup (HFCS), making it essential to determine the short\u2010 and long\u2010term effects of HFCS during this vulnerable developmental window. We hypothesized that HFCS exposure during adolescence significantly impairs hepatic metabolic signalling pathways and alters gut microbial composition, contributing to changes in energy metabolism with sex\u2010specific effects. C57bl\/6J mice with free access to HFCS during adolescence (3\u20136\u00a0weeks of age) underwent glucose tolerance and body composition testing and hepatic metabolomics, gene expression and triglyceride content analysis at 6 and 30\u00a0weeks of age (<jats:italic>n<\/jats:italic>\u00a0=\u00a06\u20138 per sex). At 6\u00a0weeks HFCS\u2010exposed mice had significant increases in fat mass, glucose intolerance, hepatic triglycerides (females) and <jats:italic>de novo<\/jats:italic> lipogenesis gene expression (ACC, DGAT, FAS, ChREBP, SCD, SREBP, CPT and PPAR\u03b1) with sex\u2010specific effects. At 30\u00a0weeks, HFCS\u2010exposed mice also had abnormalities in glucose tolerance (males) and fat mass (females). HFCS exposure enriched carbohydrate, amino acid, long chain fatty acid and secondary bile acid metabolism at 6\u00a0weeks with changes in secondary bile metabolism at 6 and 30\u00a0weeks. Microbiome studies performed immediately before and after HFCS exposure identified profound shifts of microbial species in male mice only. In summary, short\u2010term HFCS exposure during adolescence induces fatty liver, alters important metabolic pathways, some of which continue to be altered in adulthood, and changes the microbiome in a sex\u2010specific manner.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp280034","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:32:06Z","timestamp":1610757126000},"page":"1487-1511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Exposure to high fructose corn syrup during adolescence in the mouse alters hepatic metabolism and the microbiome in a sex\u2010specific manner"],"prefix":"10.1113","volume":"599","author":[{"given":"Shazia F.","family":"Bhat","sequence":"first","affiliation":[{"name":"Department of Pediatrics Christiana Care Health System  Newark DE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara 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