High-fat diet exacerbates MPTP-induced dopaminergic degeneration in mice.

Publication Type:

Journal Article


Neurobiol Dis, Volume 45, Issue 1, p.529-38 (2012)


1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Chemokine CCL2, Chemokine CCL3, Corpus Striatum, Diet, High-Fat, Dopamine, Dopaminergic Neurons, Insulin, Insulin Resistance, Interleukin-1alpha, Mice, Nerve Degeneration, Substantia Nigra


<p>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.</p>

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