Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques
Abstract The cellular mechanisms underlying a greater risk of cardiometabolic disease in adult offspring exposed to maternal obesity are not known. Our prior work found reduced skeletal muscle mitochondrial metabolism and insulin sensitivity in offspring exposed to maternal (m) Western-style diet (W...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-00828-3 |
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| author | Emily A. Beck Byron Hetrick Luis Nassar Douglas W. Turnbull Tyler A. Dean Diana L. Takahashi Maureen Gannon Stephanie R. Wesolowski Kjersti M. Aagaard Jacob E. Friedman Paul Kievit Carrie E. McCurdy |
| author_facet | Emily A. Beck Byron Hetrick Luis Nassar Douglas W. Turnbull Tyler A. Dean Diana L. Takahashi Maureen Gannon Stephanie R. Wesolowski Kjersti M. Aagaard Jacob E. Friedman Paul Kievit Carrie E. McCurdy |
| author_sort | Emily A. Beck |
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| description | Abstract The cellular mechanisms underlying a greater risk of cardiometabolic disease in adult offspring exposed to maternal obesity are not known. Our prior work found reduced skeletal muscle mitochondrial metabolism and insulin sensitivity in offspring exposed to maternal (m) Western-style diet (WD), even when weaned onto a control diet (CD) in Japanese macaques. Here, we performed multiple comparisons of differentially expressed (DE) genes in skeletal muscle from lean juvenile offspring to test hypotheses specific to (1) the lasting effects of maternal diet composition and/or maternal adiposity on gene expression and (2) the transcriptional response to a chronic postweaning (pw)WD with and without prior exposure to mWD. Overall, we identified maternal (m)WD, and not maternal adiposity, as a principal driver of DE in offspring muscle even years after exposure with few differences observed in patterns of DE between offspring of lean vs. obese mWD dams. Transcriptional response to the pwWD was robust in mCD offspring but blunted by mWD, particularly in males, suggesting a potential priming of gene expression. KEGG enrichment analysis and assessment of top DE genes identified changes in key pathways associated with dysregulated metabolism and RNA processing. We conclude that mWD has a significant and lasting impact on offspring gene expression which likely contributes to observed skeletal muscle insulin resistance and metabolic dysregulation in these offspring. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-d3cbb2dfa6644ba087b8b6626672bc7c2025-08-20T03:37:20ZengNature PortfolioScientific Reports2045-23222025-07-0115111710.1038/s41598-025-00828-3Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaquesEmily A. Beck0Byron Hetrick1Luis Nassar2Douglas W. Turnbull3Tyler A. Dean4Diana L. Takahashi5Maureen Gannon6Stephanie R. Wesolowski7Kjersti M. Aagaard8Jacob E. Friedman9Paul Kievit10Carrie E. McCurdy11Department of Data Science, University of OregonDepartment of Human Physiology, 1248 University of OregonPhil and Penny Knight Campus for Accelerating Scientific Impact, University of OregonGenomics and Cell Characterization Core Facility, University of OregonDivision of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health Science UniversityDivision of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health Science UniversityDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical CenterDepartment of Pediatrics, Perinatal Research Center, University of ColoradoTN and HCA Texas Maternal Fetal Medicine, HCA Healthcare and HCA Healthcare Research Institute NashvilleHarold Hamm Diabetes Center, University of Oklahoma Health Sciences CenterDivision of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health Science UniversityDepartment of Human Physiology, 1248 University of OregonAbstract The cellular mechanisms underlying a greater risk of cardiometabolic disease in adult offspring exposed to maternal obesity are not known. Our prior work found reduced skeletal muscle mitochondrial metabolism and insulin sensitivity in offspring exposed to maternal (m) Western-style diet (WD), even when weaned onto a control diet (CD) in Japanese macaques. Here, we performed multiple comparisons of differentially expressed (DE) genes in skeletal muscle from lean juvenile offspring to test hypotheses specific to (1) the lasting effects of maternal diet composition and/or maternal adiposity on gene expression and (2) the transcriptional response to a chronic postweaning (pw)WD with and without prior exposure to mWD. Overall, we identified maternal (m)WD, and not maternal adiposity, as a principal driver of DE in offspring muscle even years after exposure with few differences observed in patterns of DE between offspring of lean vs. obese mWD dams. Transcriptional response to the pwWD was robust in mCD offspring but blunted by mWD, particularly in males, suggesting a potential priming of gene expression. KEGG enrichment analysis and assessment of top DE genes identified changes in key pathways associated with dysregulated metabolism and RNA processing. We conclude that mWD has a significant and lasting impact on offspring gene expression which likely contributes to observed skeletal muscle insulin resistance and metabolic dysregulation in these offspring.https://doi.org/10.1038/s41598-025-00828-3Metabolic programmingMaternal dietOffspringSkeletal muscleGene expressionMaternal obesity |
| spellingShingle | Emily A. Beck Byron Hetrick Luis Nassar Douglas W. Turnbull Tyler A. Dean Diana L. Takahashi Maureen Gannon Stephanie R. Wesolowski Kjersti M. Aagaard Jacob E. Friedman Paul Kievit Carrie E. McCurdy Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques Scientific Reports Metabolic programming Maternal diet Offspring Skeletal muscle Gene expression Maternal obesity |
| title | Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques |
| title_full | Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques |
| title_fullStr | Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques |
| title_full_unstemmed | Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques |
| title_short | Maternal Western-style diet has a persistent effect on offspring gene expression in skeletal muscle of Japanese macaques |
| title_sort | maternal western style diet has a persistent effect on offspring gene expression in skeletal muscle of japanese macaques |
| topic | Metabolic programming Maternal diet Offspring Skeletal muscle Gene expression Maternal obesity |
| url | https://doi.org/10.1038/s41598-025-00828-3 |
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