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Adipocyte and Cell Biology

Maternal monosodium glutamate exposure disrupts leptin and insulin signaling in the hypothalamus, activating NF-κB and mTOR inflammatory pathways, contributing to metabolic dysfunction in male offspring

International Journal of Obesity volume 50, pages 238–259 (2026)Cite this article

Subjects

Abstract

Background

Maternal nutrition during critical developmental windows is increasingly recognised as a key determinant of offspring health, a concept central to the developmental origins of health and disease paradigm. Monosodium glutamate (MSG), a common food additive and neuroendocrine stimulant, warrants investigation in this context.

Methods

The impact of maternal MSG exposure (120 mg/kg) during gestation and/or lactation on metabolic programming in first-generation male rat offspring. Metabolic, hormonal, and molecular parameters in pups following maternal MSG administration, body weight, food intake, adiposity, glucose homeostasis (insulin sensitivity and resistance), lipid profiles, oxidative stress markers, and inflammatory mediators were measured. Furthermore, we analyzed microRNA expression profiles in relevant tissues.

Results

Maternal MSG exposure resulted in significant metabolic perturbations in offspring. Key findings included a reduced survival index, impaired glucose homeostasis (manifesting as decreased insulin sensitivity and increased insulin resistance), increased body weight, and elevated adiposity. We observed elevated oxidative stress, dyslipidemia, altered lipid peroxidation, and hormonal imbalances. Quantitative PCR analysis revealed altered expression of metabolic and inflammatory genes in both adipocytes and the hypothalamus. MicroRNA expression analysis identified significant alterations in miR-27a, miR-34a, miR-335, and miR-30a, suggesting potential regulatory roles in adipogenesis and metabolic control.

Conclusions

Maternal MSG exposure during gestation and lactation induces profound and adverse metabolic effects in male offspring. The observed alterations in metabolic indices suggest an increased risk of metabolic disease later in life. This study underscores the critical importance of maternal nutrition during sensitive developmental periods and has implications for public health recommendations and nutritional guidelines (Graphical abstract).

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Fig. 1
Fig. 2: Effect of MSG on oxidative stress markers in plasma.
Fig. 3: Effect of MSG on erythrocyte antioxidant enzymes and oxidized glutathione.
Fig. 4: Effect of MSG on erythrocyte antioxidant status.
Fig. 5: Effect of MSG on plasma metabolic parameters.
Fig. 6: Effect of MSG on plasma lipid profile and fatty acids.
Fig. 7: Effect of MSG on plasma hormone levels.
Fig. 8: Effect of MSG on plasma levels of apolipoproteins, inflammatory markers, and metabolic hormones.
Fig. 9: Effect of MSG on adipocyte cytokine and chemokine levels.
Fig. 10: Effect of MSG on adipocyte protein levels and mRNA expression of regulatory genes.
Fig. 11: Effect of MSG on adipocyte protein levels and mRNA expression of key regulatory genes.
Fig. 12: Effect of MSG on adipocyte mRNA expression of key metabolic and inflammatory genes.
Fig. 13: Effect of MSG on hypothalamic mRNA expression of key regulatory genes.
Fig. 14: Effect of MSG on adipocyte microRNA expression.

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Data availability

Data are available upon reasonable request to the corresponding author.

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Acknowledgements

The authors extend their appreciation to the Deanship of Research and Graduate Studies at King Khalid University for funding this work through Large Research Project under grant number RGP2/536/46.

Funding

This work was funded by the Deanship of Research and Graduate Studies at King Khalid University through Large Research Project under grant number RGP2/536/46.

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Authors and Affiliations

  1. Endocrinology and diabetes section, Internal Medicine Department, College of Medicine, King Khalid University, Abha, Saudi Arabia

    Alshehri Hanan Hassan

  2. Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia

    Eman Mohamad El Nashar

  3. Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia

    Norah Saeed Al-Zahrani

  4. Department of Physiology, Faculty of Medicine, King Khalid University, Abha, Saudi Arabia

    Hind Zafrah

  5. Technology of Medical Laboratory Department, Faculty of Technology of Applied Health Sciences, October 6 University, Giza, Egypt

    Hanan M. A. El Henafy

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Contributions

HHA contributed to the conceptualization, supervision, and funding acquisition. EMEN contributed to the methodology, investigation, and data analysis. NSA-Z contributed to the investigation and resources. HZ contributed to the investigation and resources. HEH contributed to the conceptualization, methodology, investigation, data analysis, and writing of the manuscript.

Corresponding authors

Correspondence to Eman Mohamad El Nashar or Hanan M. A. El Henafy.

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The authors declare no competing interests.

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The experimental protocol was approved by the Ethical Committee of the Atomic Energy Authority, Egypt (Approval No. 85-23). All methods were performed in accordance with the relevant guidelines and regulations and complied with the “Guide for the Care and Use of Laboratory Animals” published by the U.S. National Institutes of Health (NIH Publication No. 85-23, 1996).

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Hassan, A.H., El Nashar, E.M., Al-Zahrani, N.S. et al. Maternal monosodium glutamate exposure disrupts leptin and insulin signaling in the hypothalamus, activating NF-κB and mTOR inflammatory pathways, contributing to metabolic dysfunction in male offspring. Int J Obes 50, 238–259 (2026). https://doi.org/10.1038/s41366-025-01941-z

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