{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:36:32Z","timestamp":1790742992896,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T00:00:00Z","timestamp":1455667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,3,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Postnatal intake of a high saturated fat\/high sugar diet, the Western diet (WD), is a risk factor for liver fibrosis. Recently, adverse <jats:italic>in utero<\/jats:italic> conditions resulting in low birth weight (LBW) have also been associated with postnatal fibrosis development.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We demonstrate that suboptimal <jats:italic>in utero<\/jats:italic> conditions resulting in LBW are associated with changes in hepatic profibrotic genes in conjunction with minimal liver fibrosis in young non\u2010overweight adult guinea pigs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results also indicate that WD promotes liver steatosis, enhanced expression of hepatic genes and proteins of the proinflammatory, profibrotic, cell death and collagen deposition pathways in conjunction with mild hepatic fibrosis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data highlight that pathways responsible for the initiation of a profibrotic state and ultimately hepatic fibrosis appear different depending upon the insult, an <jats:italic>in utero<\/jats:italic>\u2010induced LBW outcome or a postnatal WD exposure.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Postnatal intake of an energy dense diet, the Western diet (WD), is a strong risk factor for liver fibrosis. Recently, adverse <jats:italic>in utero<\/jats:italic> conditions resulting in low birth weight (LBW) have also been associated with postnatal fibrosis development. We assessed the independent and possible synergistic effects of placental insufficiency\u2010induced LBW and postnatal WD consumption on liver fibrosis in early adulthood, with a specific focus on changes in inflammation and apoptosis pathways in association with fibrogenesis. Male LBW (uterine artery ablation) and normal birth weight (NBW) guinea pig pups were fed either a control diet (CD) or WD from weaning to 150\u00a0days. Significant steatosis, mild lobular inflammation, apoptosis and mild stage 1 fibrosis (perisinusoidal or portal) were evident in WD\u2010fed offspring (NBW\/WD and LBW\/WD). In LBW\/CD <jats:italic>versus<\/jats:italic> NBW\/CD offspring, increased transforming growth factor\u2010beta 1 and matrix metallopeptidase mRNA and sma\u2010 and Mad\u2010related protein 4 (SMAD4) were present in conjunction with minimal stage 1 portal fibrosis. Further, connective tissue growth factor mRNA was increased and miR\u2010146a expression decreased in LBW offspring, irrespective of diet. Independent of birth weight, WD\u2010fed offspring exhibited increased expression of fibrotic genes as well as elevated inflammatory and apoptotic markers. Moreover, the augmented expression of collagen, type III, alpha 1 and tumor necrosis factor\u2010alpha was associated with increased recruitment of RNA polymerase II and enhanced histone acetylation (K9) to their respective promoters. These data support a role for both LBW and postnatal WD as factors contributing to hepatic fibrosis development in offspring through distinct pathways.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp271777","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T11:17:42Z","timestamp":1449746262000},"page":"1753-1772","source":"Crossref","is-referenced-by-count":32,"title":["The differential effects of low birth weight and Western diet consumption upon early life hepatic fibrosis development in guinea pig"],"prefix":"10.1113","volume":"594","author":[{"given":"Ousseynou","family":"Sarr","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Western University  1151 Richmond Street London ON Canada N6A 5C1"},{"name":"Lawson Research Institute  268 Grosvenor St London ON Canada N6A 4V2"},{"name":"Children's Health Research Institute  800 Commissioners Road East London ON Canada N6C 2V5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Blake","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  1151 Richmond Street London ON Canada N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  1151 Richmond Street London ON Canada N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Western University  1151 Richmond Street London ON Canada N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Rabicki","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Western University  1151 Richmond Street London ON Canada N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna C.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine Western University  1151 Richmond Street London ON Canada N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Welch","sequence":"additional","affiliation":[{"name":"Animal Care and Veterinary Services Western University  1151 Richmond Street London ON Canada N6A 5C1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R. 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