title: High-fat diet feeding differentially affects the development of inflammation in the central nervous system.
abstract: Obesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone.
  
  
  
  We used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet. We also performed a large-scale analysis of lipids in the central nervous system using HPLC-MS, and we then tested the lipids of interest on a primary co-culture of astrocytes and microglial cells.
  
  
  
  We measured an increase in the inflammatory tone in the cerebellum at the different time-points. However, at week 16, we evidenced that the inflammatory tone displayed significant differences in two different regions of the central nervous system, specifically an increase in the cerebellum and no modification in the cortex for high-fat diet mice when compared with chow-fed mice. Our results clearly suggest region-dependent as well as time-dependent adaptations of the central nervous system to the high-fat diet. The differences in inflammatory tone between the two regions considered seem to involve astrocytes but not microglial cells. Furthermore, a large-scale lipid screening coupled to ex vivo testing enabled us to identify three classes of lipids-phosphatidylinositols, phosphatidylethanolamines, and lysophosphatidylcholines-as well as palmitoylethanolamide, as potentially responsible for the difference in inflammatory tone.
  
  
  
  This study demonstrates that the inflammatory tone induced by a high-fat diet does not similarly affect distinct regions of the central nervous system. Moreover, the lipids identified and tested ex vivo showed interesting anti-inflammatory properties and could be further studied to better characterize their activity and their role in controlling inflammation in the central nervous system.
authors: Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCL), Av. E.Mounier, 72 (B1.72.01), 1200, Brussels, Belgium.
authors: Owein
authors: O
authors: Guillemot-Legris
authors: Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCL), Av. E.Mounier, 72 (B1.72.01), 1200, Brussels, Belgium.
authors: Julien
authors: J
authors: Masquelier
authors: Metabolism and Nutrition Research Group, WELBIO - Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors: Amandine
authors: A
authors: Everard
authors: Metabolism and Nutrition Research Group, WELBIO - Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors: Patrice D
authors: PD
authors: Cani
authors: Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCL), Av. E.Mounier, 72 (B1.72.01), 1200, Brussels, Belgium.
authors: Mireille
authors: M
authors: Alhouayek
authors: Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute (LDRI), Université catholique de Louvain (UCL), Av. E.Mounier, 72 (B1.72.01), 1200, Brussels, Belgium. giulio.muccioli@uclouvain.be.
authors: Giulio G
authors: GG
authors: Muccioli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D002784:Cholesterol / Q000378:metabolism; D003469:Culture; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D050356:Lipid Metabolism / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009765:Obesity / Q000209:etiology*; D013997:Time Factors
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D002784:Cholesterol
keywords: Astrocyte; Bioactive lipid; Cerebellum; Cortex; HPLC-MS; Microglia; Obesity; PEA