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Gestational low-protein diet impairs mitochondrial function and skeletal muscle development by inducing immune responses in male offspring
Altinpinar, Atilla Emre Alameddine, Moussira Ersoy, Ufuk Kanakis, Ioannis Pekovic-Vaughan, Vanja Ozanne, Susan E. Goljanek-Whysall, Katarzyna Vasilaki, Aphrodite
Altinpinar, Atilla Emre
Alameddine, Moussira
Ersoy, Ufuk
Kanakis, Ioannis
Pekovic-Vaughan, Vanja
Ozanne, Susan E.
Goljanek-Whysall, Katarzyna
Vasilaki, Aphrodite
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2025-10-10
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Abstract
Maternal nutrition is essential for proper fetal and postnatal organ maturation and is linked to the future risk of developing metabolic syndrome, cardiovascular disease, and muscle loss. There is still limited understanding how a low-protein intake during gestation influences skeletal muscle development, inflammation, and the related pathways. This study aimed to investigate the impact of gestational low-protein diet in mice on skeletal muscle development and inflammatory responses in male offspring. Pups born from mothers fed a low-protein diet (LPD) were lactated by normal protein diet (NPD)-fed mothers and maintained on NPD post-weaning (LNN group). Offspring born from mothers fed an NPD and maintained on an NPD during lactation and beyond were used as controls (NNN group). In 21-day-old offspring from protein-restricted mothers, RNA-Seq analysis showed upregulation of immune response–related genes, enriching adaptive immunity pathways. Additionally, LNN group exhibited elevated markers of inflammation, along with disruptions in antioxidant defence balance and macrophages infiltration in gastrocnemius muscle at 3 months of age. Energy metabolism was impaired, as indicated by changes in related proteins and enzymes involved in mitochondrial function. We conclude that gestational LPD adversely affects skeletal muscle development in male offspring.
Citation
Altinpinar, A. E., Alameddine, M., Ersoy, U., Kanakis, I., Pekovic-Vaughan, V., Ozanne, S. E., Goljanek-Whysall, K., & Vasilaki, A. (2025). Gestational low-protein diet impairs mitochondrial function and skeletal muscle development by inducing immune responses in male offspring. Redox Biology, 87, article-number 103890. https://doi.org/10.1016/j.redox.2025.103890
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Elsevier
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Redox Biology
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Article
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en
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© 2025 The Authors. Published by Elsevier B.V.
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2213-2317
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Biotechnology and Biological Sciences Research Council (grant numbers BBSRC; (BB/P008429/1 and BB/W018276/1). Republic of Türkiye Ministry of National Education. The authors disclose support for this work from the University of Liverpool.