title: High-fat diet exacerbates MPTP-induced dopaminergic degeneration in mice.
abstract: The identification of modifiable nutritional risk factors is highly relevant to the development of preventive strategies for neurodegenerative disorders including Parkinson's disease (PD). In this study, adult C57BL/6 mice were fed either a control (CD-12%kcal) or a high-fat diet (HFD-60%kcal) for 8 weeks prior to MPTP exposure, a toxin which recreates a number of pathological features of PD. HFD-fed mice significantly gained weight (+41%), developed insulin resistance and a systemic immune response characterized by an increase in circulating leukocytes and plasmatic cytokines/chemokines (interleukin-1α, MCP-1, MIP-1α). As expected, the MPTP treatment produced nigral dopaminergic degeneration as evidenced by the loss of striatal dopamine and the decreased number of nigral tyrosine hydroxylase (TH)- and dopamine transporter-expressing neurons (23% and 25%, respectively). However, exposure to HFD exacerbated the effects of MPTP on striatal TH (23%) and dopamine levels (32%), indicating that diet-induced obesity is associated with a reduced capacity of nigral dopaminergic terminals to cope with MPTP-induced neurotoxicity. Since high-fat consumption is commonplace in our modern society, dietary fat intake may represent an important modifiable risk factor for PD.
authors.affiliation: Centre de Recherche du CHUL (CHUQ), Axe Neurosciences, Québec, QC, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Bousquet
authors.forename: I
authors.initials: I
authors.lastname: St-Amour
authors.forename: M
authors.initials: M
authors.lastname: Vandal
authors.forename: P
authors.initials: P
authors.lastname: Julien
authors.forename: F
authors.initials: F
authors.lastname: Cicchetti
authors.forename: F
authors.initials: F
authors.lastname: Calon
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D053582:Interleukin-1alpha / Q000097:blood; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D007328:Insulin; D053582:Interleukin-1alpha; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine