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High-fat diet consumption alters energy metabolism in the mouse hypothalamus

International Journal of Obesity volume 43, pages 1295–1304 (2019)Cite this article

Subjects

Abstract

Background/Objectives

High-fat diet consumption is known to trigger an inflammatory response in the hypothalamus, which has been characterized by an initial expression of pro-inflammatory genes followed by hypothalamic astrocytosis, microgliosis, and the appearance of neuronal injury markers. The specific effects of high-fat diet on hypothalamic energy metabolism and neurotransmission are however not yet known and have not been investigated before.

Subjects/Methods

We used 1H and 13C magnetic resonance spectroscopy (MRS) and immunofluorescence techniques to evaluate in vivo the consequences of high-saturated fat diet administration to mice, and explored the effects on hypothalamic metabolism in three mouse cohorts at different time points for up to 4 months.

Results

We found that high-fat diet increases significantly the hypothalamic levels of glucose (P < 0.001), osmolytes (P < 0.001), and neurotransmitters (P < 0.05) from 2 months of diet, and alters the rates of metabolic (P < 0.05) and neurotransmission fluxes (P < 0.001), and the contribution of non-glycolytic substrates to hypothalamic metabolism (P < 0.05) after 10 weeks of high-fat feeding.

Conclusions/interpretation

We report changes that reveal a high-fat diet-induced alteration of hypothalamic metabolism and neurotransmission that is quantifiable by 1H and 13C MRS in vivo, and present the first evidence of the extension of the inflammation pathology to a localized metabolic imbalance.

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Acknowledgements

This research was supported by the Swiss National Science Foundation (grants 148250 to JMND, and 149983 to RG), and by Centre d’Imagerie BioMédicale (CIBM) of the UNIL, UNIGE, HUG, CHUV, EPFL, and the Leenaards and Jeantet Foundations. JMND acknowledges the generous support from the Knut and Alice Wallenberg foundation. We thank A.F. Soares for helping designing the diet administration protocol and monitoring the animals and H. Lei for her technical support. BL designed the study, performed experiments, and wrote the manuscript. AC and JMND performed experiments, and all authors contributed to interpreting the data and writing the manuscript. BL takes full responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Blanca Lizarbe, Antoine Cherix, João M. N. Duarte & Rolf Gruetter

  2. Department of Experimental Medical Science, Faculty of Medicine, Lund University, Lund, Sweden

    João M. N. Duarte

  3. Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden

    João M. N. Duarte

  4. Center for Psychiatric Neuroscience (CNP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    Jean-René Cardinaux

  5. Department of Radiology, University of Geneva, Geneva, Switzerland

    Rolf Gruetter

  6. Department of Radiology, University of Lausanne, Lausanne, Switzerland

    Rolf Gruetter

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  1. Blanca Lizarbe
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Correspondence to Blanca Lizarbe.

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Lizarbe, B., Cherix, A., Duarte, J.M.N. et al. High-fat diet consumption alters energy metabolism in the mouse hypothalamus. Int J Obes 43, 1295–1304 (2019). https://doi.org/10.1038/s41366-018-0224-9

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