{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T10:00:23Z","timestamp":1766138423921,"version":"3.41.2"},"reference-count":18,"publisher":"Portland Press Ltd.","issue":"10","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["162452"],"award-info":[{"award-number":["162452"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["G-19-0026536"],"award-info":[{"award-number":["G-19-0026536"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: Exposure to high maternal adiposity in utero is a significant risk factor for the later-life development of metabolic syndrome (MetS), including non-alcoholic fatty liver disease (NAFLD). We have previously shown that high pre-pregnancy adiposity programs adipose tissue dysfunction in the offspring, leading to spillover of fatty acids into the circulation, a key pathogenic event in obesity-associated MetS. Herein, we hypothesized that programming of adipose tissue dysfunction in offspring born to overweight dams increases the risk for developing NAFLD. Results: Females heterozygous for leptin receptor deficiency (Hetdb) were used as a model of high pre-pregnancy adiposity. Female wild-type (Wt) offspring born to Hetdb pregnancies gained significantly more body fat following high-fat\/fructose diet (HFFD) compared with Wt offspring born to Wt dams. HFFD increased circulating free fatty acids (FFA) in male offspring of control dams, while FFA levels were similar in HFFD-fed offspring from Wt dams and CD or HFFD-fed Wt offspring from Hetdb dams. Despite female-specific protection from diet-induced FFA spillover, both male and female offspring from Hetdb dams were more susceptible to diet-induced hepatosteatosis. Lipidomic analysis revealed that CD-offspring of overweight dams had decreased hepatic polyunsaturated FA (PUFA) levels compared with control offspring. Changes to saturated FA (SFA) and the de novo lipogenic (DNL) index were diet driven; however, there was a significant effect of the intrauterine environment on FA elongation and \u03949 desaturase activity. Conclusion: High maternal adiposity during pregnancy programs a susceptibility to diet-induced hepatosteatosis.<\/jats:p>","DOI":"10.1042\/bsr20231060","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:12:46Z","timestamp":1694697166000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["High maternal adiposity during pregnancy programs an imbalance in the lipidome and predisposes to diet-induced hepatosteatosis in the offspring"],"prefix":"10.1042","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0642-4109","authenticated-orcid":false,"given":"Taylor\u00a0B.","family":"Scheidl","sequence":"first","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada"},{"name":"2Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"3Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"4Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica\u00a0L.","family":"Wager","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada"},{"name":"2Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"3Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa\u00a0G.","family":"Baker","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada"},{"name":"2Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy\u00a0L.","family":"Brightwell","sequence":"additional","affiliation":[{"name":"5Department of Biological Sciences, University of Calgary, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina\u00a0M.","family":"Melan","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Larion","sequence":"additional","affiliation":[{"name":"6Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ousseynou","family":"Sarr","sequence":"additional","affiliation":[{"name":"7Departments of Obstetrics and Gynaecology and Physiology and Pharmacology, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy\u00a0RH.","family":"Regnault","sequence":"additional","affiliation":[{"name":"7Departments of Obstetrics and Gynaecology and Physiology and Pharmacology, Western University, London, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan\u00a0J.","family":"Urbanski","sequence":"additional","affiliation":[{"name":"8Department of Pathology, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0421-3719","authenticated-orcid":false,"given":"Jennifer\u00a0A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada"},{"name":"2Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada"},{"name":"3Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada"},{"name":"4Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"2023100309105088000_B1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. 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