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

Research output: Contribution to journalArticle


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.


External organisations
  • Swiss Federal Institute of Technology
  • Lausanne University Hospital
  • University of Geneva
  • University of Lausanne
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Physiology
  • Nutrition and Dietetics
Original languageEnglish
Pages (from-to)1295-1304
JournalInternational Journal of Obesity
Issue number6
Early online date2018 Sep 9
Publication statusPublished - 2019
Publication categoryResearch