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Open AccessArticle

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

1
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
2
Department of Pediatrics, E-DA Hospital, Kaohsiung 82445, Taiwan
3
Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
4
Division of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 207; https://doi.org/10.3390/ijms21010207
Received: 8 November 2019 / Revised: 16 December 2019 / Accepted: 23 December 2019 / Published: 27 December 2019
Although several epidemiologic and animal studies have revealed correlations between obesity and neurodegenerative disorders, such as Parkinson disease (PD), the underlying pathological mechanisms of obesity-induced PD remain unclear. Our study aimed to assess the effect of diet-induced obesity on the brain dopaminergic pathway. For five months, starting from weaning, we gave C57BL/6 mice a high-fat diet (HFD) to generate an obese mouse model and investigate whether the diet reprogrammed the midbrain dopaminergic system. Tyrosine hydroxylase staining showed that the HFD resulted in fewer dopaminergic neurons in the substantia nigra (SN), but not the striatum. It also induced neuroinflammation, with increased astrogliosis in the SN and striatum. Dendritic spine density in the SN of HFD-exposed mice decreased, which suggested that prolonged HFD altered dopaminergic neuroplasticity. All three peroxisome proliferator-activated receptor (PPAR) subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area of HFD mice when compared to those in controls. This study showed that a prolonged HFD induced neuroinflammation, suppressed PPAR levels, caused degeneration of midbrain dopaminergic neurons, and resulted in symptoms reminiscent of human PD. To our knowledge, this is the first study documenting the effects of an HFD on PPARs in dopaminergic neurons. View Full-Text
Keywords: high-fat diet (HFD); dopamine (DA); Parkinson disease (PD); peroxisome proliferator-activated receptor (PPAR) high-fat diet (HFD); dopamine (DA); Parkinson disease (PD); peroxisome proliferator-activated receptor (PPAR)
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Kao, Y.-C.; Wei, W.-Y.; Tsai, K.-J.; Wang, L.-C. High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra. Int. J. Mol. Sci. 2020, 21, 207.

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