{
  "abstract": "Background Weight loss is a substantial non-motor feature of Parkinson’s disease (PD) associated with worse clinical outcomes, but the underlying mechanisms remain poorly understood. Thus, we investigated the mechanisms of PD-related weight loss by examining the correlation between body composition and various plasma metabolites.Methods We enrolled 91 patients with PD and 47 healthy controls between July 2021 and October 2023. Body composition was evaluated using bioelectrical impedance analysis. Plasma metabolite profiling was conducted via mass spectrometry, including short-chain and medium-chain fatty acids, Krebs cycle intermediates, ketone bodies and phospholipids. Subsequently, alterations in body composition in PD and their association with plasma metabolites were assessed.Results Patients with PD had lower body weight (p=0.003), body mass index (BMI; p=0.001) and body fat mass (p<0.001) compared with controls. Metabolomic analyses revealed that, in patients with PD, glycolysis and Krebs cycle markers (lactic acid and succinic acid) were reduced, while ketone bodies (acetoacetic acid and 3-hydroxybutyric acid), amino acid catabolism-related markers (2-hydroxybutyric acid and 2-oxobutyric acid) and acetic acid were elevated. Notably, in patients with PD, acetoacetic acid and 3-hydroxybutyric acid negatively correlated with BMI. Phosphatidylcholine (40:2) was also elevated in PD and showed higher levels in individuals at more advanced Hoehn and Yahr stages.Conclusions PD-related fat loss was accompanied by a pattern of lower glycolytic activity and higher levels of lipid and amino acid metabolism-related metabolites, consistent with a potential shift in energy utilisation. These findings highlight metabolic pathways as potential targets for interventions to mitigate weight loss in PD.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan",
        "Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Japan"
      ],
      "name": "Atsuhiro Higashi"
    },
    {
      "affiliations": [
        "Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Yasuaki Mizutani"
    },
    {
      "affiliations": [
        "Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Reiko Ohdake"
    },
    {
      "affiliations": [
        "Open Facility Center, Fujita Health University, Toyoake, Japan"
      ],
      "name": "Yasuhiro Maeda"
    },
    {
      "affiliations": [
        "Department of Biomedical Data Science, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Junichiro Yoshimoto"
    },
    {
      "affiliations": [
        "Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Sayuri Shima"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Diabetes and Metabolism, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Yusuke Seino"
    },
    {
      "affiliations": [
        "Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Akihiro Ueda"
    },
    {
      "affiliations": [
        "Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Mizuki Ito"
    },
    {
      "affiliations": [
        "Department of Endocrinology, Diabetes and Metabolism, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Atsushi Suzuki"
    },
    {
      "affiliations": [
        "Department of Neurology, Fujita Health University School of Medicine, Toyoake, Japan"
      ],
      "name": "Hirohisa Watanabe"
    }
  ],
  "title": "Metabolic profiles associated with fat loss in Parkinson’s disease",
  "uid": "4e6558d2-7eb8-5694-95ad-322443667046"
}