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We hypothesized that maternal nutrient excess leads to fetal inflammation and impairs offspring skeletal muscle mitochondrial biogenesis in non-human primates. At least 12 months before pregnancy, female baboons were fed a normal chow (CTR, 12% energy fat) or a maternal nutrient excess (MNE, 45% energy fat, and ad libitum fructose sodas) diet, with the latter to induce obesity. After 165 days of gestation (0.9 G), offspring baboons were delivered by cesarean section, and the soleus muscle was collected (CTR n = 16, MNE n = 5). At conception, MNE mothers presented increased body fat and weighed more than controls. The soleus muscle of MNE fetuses exhibited increased levels of stress signaling associated with inflammation (TLR4, TNF\u03b1, NF-kB p65, and p38), concomitant with reduced expression of key regulators of mitochondrial biogenesis, including PGC1\u03b1, both at the protein and transcript levels, as well as downregulation of PPARGC1B, PPARA, PPARB, CREB1, NOS3, SIRT1, SIRT3. Decreased transcript levels of NRF1 were observed alongside diminished mitochondrial DNA copy number, mitochondrial fusion elements (MFN1, MFN2), cytochrome C protein levels, and cytochrome C oxidase subunits I and II transcripts (cox1 and cox2). MNE coupled to MO-induced stress signaling in fetal baboon soleus muscle is associated with impaired mitochondrial biogenesis and lower mitochondrial content, resembling the changes observed in metabolic dysfunctions, such as diabetes. The observed fetal alterations may have important implications for postnatal development and metabolism, potentially increasing the risk of early-onset metabolic disorders and other non-communicable diseases.<\/jats:p>","DOI":"10.3390\/biology14070868","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T13:00:51Z","timestamp":1752757251000},"page":"868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Maternal Nutrient Excess Induces Stress Signaling and Decreases Mitochondrial Number in Term Fetal Baboon Skeletal Muscle"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-4210","authenticated-orcid":false,"given":"Xu","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA"},{"name":"Institute for Health and Sport, Victoria University, Melbourne, VIC 8001, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-0454","authenticated-orcid":false,"given":"Carolina","family":"Tocantins","sequence":"additional","affiliation":[{"name":"CNC-UC, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"CIBB, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"PDBEB\u2014Doctoral Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research, University of Coimbra, 3004-517 Coimbra, Portugal"}]},{"given":"Mei-Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA"},{"name":"School of Food Science, Washington State University, Pullman, WA 99164, USA"}]},{"given":"Susana P.","family":"Pereira","sequence":"additional","affiliation":[{"name":"CNC-UC, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"CIBB, Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-531 Coimbra, Portugal"},{"name":"UCIBIO, Applied Molecular Biosciences Unit, Department of Chemistry, Faculty of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7232-072X","authenticated-orcid":false,"given":"Min","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA"},{"name":"Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","article-title":"Obesity: Global Epidemiology and Pathogenesis","volume":"15","year":"2019","journal-title":"Nat. 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