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PALD occur in approximately 3% of pregnancies and are characterized by maternal hepatic oxidative stress (OS) and mitochondrial dysfunction. Maternal hepatic disease increases maternal and fetal morbidity and mortality. Understanding the role of MO on liver function and pathophysiology could be crucial for better understanding the altered pathways leading to PALD and liver disease, possibly paving the way to prevention and adequate management of disease. We investigated specific hepatic metabolic alterations in mitochondria and oxidative stress during MO at late-gestation.<\/jats:p>\n               <jats:p>Maternal hepatic tissue was collected at 90% gestation in Control and MO ewes (fed 150% of recommended nutrition starting 60 days before conception). Maternal hepatic redox state, mitochondrial respiratory chain (MRC), and OS markers were investigated. MO decreased MRC complex-II activity and its subunits SDHA and SDHB protein expression, increased complex-I and complex-IV activities despite reduced complex-IV subunit mtCO1 protein expression, and increased ATP synthase ATP5A subunit. Hepatic MO-metabolic remodeling was characterized by decreased adenine nucleotide translocator 1 and 2 (ANT-1\/2) and voltage-dependent anion channel (VDAC) protein expression and protein kinase A (PKA) activity (P&amp;lt;0.01), and augmented NAD+\/NADH ratio due to reduced NADH levels (P&amp;lt;0.01). MO showed an altered redox state with increased OS, increased lipid peroxidation (P&amp;lt;0.01), decreased GSH\/GSSG ratio (P=0.005), increased superoxide dismutase (P=0.03) and decreased catalase (P=0.03) antioxidant enzymatic activities, lower catalase, glutathione peroxidase (GPX)-4 and glutathione reductase protein expression (P&amp;lt;0.05), and increased GPX-1 abundance (P=0.03). MO-related hepatic changes were more evident in the right lobe, corroborated by the integrative data analysis.<\/jats:p>\n               <jats:p>Hepatic tissue from obese pregnant ewes showed alterations in the redox state, consistent with OS and MRC and metabolism remodeling. These are hallmarks of PALD and hepatic disease, supporting MO as a risk-factor and highlighting OS and mitochondrial dysfunction as mechanisms responsible for liver disease predisposition.<\/jats:p>","DOI":"10.1042\/cs20230048","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T07:56:00Z","timestamp":1691740560000},"page":"1347-1372","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Maternal hepatic adaptations during obese pregnancy encompass lobe-specific mitochondrial alterations and oxidative stress"],"prefix":"10.1042","volume":"137","author":[{"given":"Lu\u00eds\u00a0F.","family":"Grilo","sequence":"first","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"},{"name":"2Ph.D. Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal"}]},{"given":"Jo\u00e3o\u00a0D.","family":"Martins","sequence":"additional","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"}]},{"given":"Mariana\u00a0S.","family":"Diniz","sequence":"additional","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"}]},{"given":"Carolina","family":"Tocantins","sequence":"additional","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"}]},{"given":"Chiara\u00a0H.","family":"Cavallaro","sequence":"additional","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"}]},{"given":"In\u00eas","family":"Baldeiras","sequence":"additional","affiliation":[{"name":"3Neurological Clinic, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Teresa","family":"Cunha-Oliveira","sequence":"additional","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"}]},{"given":"Stephen","family":"Ford","sequence":"additional","affiliation":[{"name":"4Department of Animal Science, University of Wyoming, Laramie, WY, U.S.A."}]},{"given":"Peter\u00a0W.","family":"Nathanielsz","sequence":"additional","affiliation":[{"name":"4Department of Animal Science, University of Wyoming, Laramie, WY, U.S.A."}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5201-9948","authenticated-orcid":false,"given":"Paulo\u00a0J.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-2444","authenticated-orcid":false,"given":"Susana\u00a0P.","family":"Pereira","sequence":"additional","affiliation":[{"name":"1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal"},{"name":"5Laboratory of Metabolism and Exercise (LametEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, Porto, Portugal"}]}],"member":"288","published-online":{"date-parts":[[2023,9,1]]},"reference":[{"key":"2023090108110537100_B1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.jand.2016.01.008","article-title":"Position of the academy of nutrition and dietetics: obesity, reproduction, and pregnancy outcomes","volume":"116","author":"Stang","year":"2016","journal-title":"J. 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