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Animal Models

Metabolic and genomic adaptations to winter fattening in a primate species, the grey mouse lemur (Microcebus murinus)

International Journal of Obesity volume 42, pages 221–230 (2018)Cite this article

Subjects

Abstract

Aim:

To understand the mechanisms underlying the development of metabolic changes leading to obesity remains a major world health issue. Among such mechanisms, seasonality is quite underestimated although it corresponds to the manifestation of extreme metabolic flexibility in response to a changing environment. Nevertheless, the changes induced by such flexibility are far to be understood, especially at the level of insulin signaling, genomic stability or inflammation.

Methods:

Here, we investigated the metabolic regulations displayed by a seasonal primate species, the grey mouse lemur (Microcebus murinus) that exhibits pronounced changes in body mass during the 6-month winter season: a fattening period followed by a spontaneous fat loss, without ever reaching pathological stages.

Results:

Such body weight modulations result from a combination of behavioral (food intake) and physiological (endocrine changes, switch between carb and lipid oxidation) adjustments that spontaneously operate during winter. Conversely to classical models of obesity, insulin sensitivity is paradoxically preserved during the obesogenic phase. Fat loss is associated with increased metabolic activity, especially in brown adipose tissue, and induced increased oxidative stress associated with telomere length dynamic. Furthermore, liver gene expression analysis revealed regulations in metabolic homeostasis (beta-oxidation, insulin signaling, cholesterol and lipid metabolism) but not for genes involved in inflammatory process (for example, Ifng, Tnf, Nfkb1).

Conclusion:

Altogether, these results show that mouse lemurs undergo deep physiological and genomic seasonal changes, without ever reaching a pathological stage. Further investigation is needed to decipher the underlying mechanisms, which may well be highly relevant for human therapeutic strategies.

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Acknowledgements

The authors are grateful to Jacques Epelbaum and Martine Perret for their invaluable editing contribution to this manuscript. This work was financed by national French programs granted by the CNRS (PEPS Exomod) and the MNHN (ATM Cycles de Vie). We warmly thank Marie-Stéphanie Clerget-Froidevaux and Isabelle Seugnet for technical support.

Author contributions

JT, JFR and FA designed the study; JT, DC and LR developed the methodologies and performed the analysis; JT, MG and VZ collected the data; JT, LR, JFR and FA wrote the manuscript.

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Authors and Affiliations

  1. UMR CNRS/MNHN 7179 MECADEV, Brunoy, France

    J Terrien, M Gaudubois, D Champeval, V Zaninotto & F Aujard

  2. UMR CNRS/MNHN 7196—INSERM U1154, Paris Cedex, France

    L Roger & J F Riou

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  1. J Terrien
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Correspondence to J Terrien.

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Terrien, J., Gaudubois, M., Champeval, D. et al. Metabolic and genomic adaptations to winter fattening in a primate species, the grey mouse lemur (Microcebus murinus). Int J Obes 42, 221–230 (2018). https://doi.org/10.1038/ijo.2017.195

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