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Early life overnutrition impairs plasticity of non-neuronal brainstem cells and drives obesity in offspring across development in rats

International Journal of Obesity volume 44, pages 2405–2418 (2020)Cite this article

Subjects

Abstract

Background

The prevalence of adolescent obesity has increased dramatically, becoming a serious public health concern. While previous evidence suggests that in utero- and early postnatal overnutrition increases adult-onset obesity risk, the neurobiological mechanisms underlying this outcome are not well understood. Non-neuronal cells play an underestimated role in the physiological responses to metabolic/nutrient signals. Hypothalamic glial-mediated inflammation is now considered a contributing factor in the development and perpetuation of obesity; however, attention on the role of gliosis and microglia activation in other nuclei is still needed.

Methods/results

Here, we demonstrate that early life consumption of high-fat/sucrose diet (HFSD) is sufficient to increase offspring body weight, hyperleptinemia and potentially maladaptive cytoarchitectural changes in the brainstem dorsal-vagal-complex (DVC), an essential energy balance processing hub, across postnatal development. Our data demonstrate that pre- and postnatal consumption of HFSD result in increased body weight, hyperleptinemia and dramatically affects the non-neuronal landscape, and therefore the plasticity of the DVC in the developing offspring.

Conclusions

Current findings are very provocative, considering the importance of the DVC in appetite regulation, suggesting that HFSD-consumption during early life may contribute to subsequent obesity risk via DVC cytoarchitectural changes.

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Fig. 1: Experimental design, body weight and energy intake of dams.
Fig. 2: Body weight and energy intake of male and female pups across development.
Fig. 3: Insulin, Leptin and GLP-1 measurements in the developing offspring.
Fig. 4: Immunohistochemistry for astroglial cells in the DVC of developing offspring.
Fig. 5: Immunohistochemistry for microglia in the DVC of developing offspring.
Fig. 6: Immunohistochemistry for tanycytes in the DVC of developing offspring.

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Acknowledgements

This research was supported by NIH-DK115762 (M.R.H.) and the Swiss National Foundation FNSNF-P22HP3_172289 (CGL). M.R.H. receives research support from Eli Lilly & Co., and Boehringer Ingelheim, none of which was used in the collection of these data.

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Authors and Affiliations

  1. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Claudia G. Liberini, Misgana Ghidewon, Tyler Ling, Rinzin Lhamo, Nina Juntereal, Lauren M. Stein & Matthew R. Hayes

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  1. Claudia G. Liberini
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Contributions

C.G.L. and M.R.H. conceptualized of and designed the experiments; C.G.L., R.L., M.G., T.L., N.J., and L.M.S. conducted the research, C.G.L. and M.R.H. analyzed the data, C.G.L. and M.R.H. wrote the manuscript, and all authors reviewed/edited the manuscript. M.R.H. is the guarantor of this work and, as such, has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Claudia G. Liberini or Matthew R. Hayes.

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Liberini, C.G., Ghidewon, M., Ling, T. et al. Early life overnutrition impairs plasticity of non-neuronal brainstem cells and drives obesity in offspring across development in rats. Int J Obes 44, 2405–2418 (2020). https://doi.org/10.1038/s41366-020-00658-5

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