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

• Published in: International Journal of Obesity Vol. 43; no. 6; pp. 1295 - 1304
• Main Authors: Lizarbe, Blanca, Cherix, Antoine, Duarte, João M. N., Cardinaux, Jean-René, Gruetter, Rolf
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2019; Nature Publishing Group
• Subjects: 59; 59/57; 631/378/1488/1562; 64/60; 692/163/2743/393; 82/51; Animals; Basic Medicine; Bioenergetics; Brain; Diet; Diet, High-Fat - adverse effects; Dietary Fats - administration & dosage; Dietary Fats - pharmacology; Disease Models, Animal; Energy metabolism; Energy Metabolism - drug effects; Epidemiology; Fluxes; Fysiologi; Fysiologi och anatomi; Gene expression; Gene Expression Profiling; Gliosis; Glycolysis; Health aspects; Health Promotion and Disease Prevention; Health Sciences; High fat diet; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Hypothalamus - physiopathology; Hälsovetenskap; Immunofluorescence; In vivo methods and tests; Inflammation; Inflammation - metabolism; Inflammatory response; Internal Medicine; Ketogenic diet; Magnetic resonance spectroscopy; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Medicinska och farmaceutiska grundvetenskaper; Metabolic Diseases; Metabolism; Mice; Mice, Inbred C57BL; Neurons - metabolism; Neurotransmission; Neurotransmitters; Nutrition and Dietetics; Näringslära; Näringslära och dietkunskap; Physiology; Physiology and Anatomy; Public Health; Rodents; Substrates
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/s41366-018-0224-9

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 1 H and 13 C 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 1 H and 13 C MRS in vivo, and present the first evidence of the extension of the inflammation pathology to a localized metabolic imbalance.