Systemic Metabolic Alteration Dependent on the Thyroid-Liver Axis in Early PD

Area of Science:

• Neuroscience
• Metabolomics
• Endocrinology

Background:

• Parkinson's disease (PD) is a neurodegenerative disorder with early autonomic dysfunction.
• The impact of PD-related dysautonomia on systemic metabolism remains largely unexplored.
• Understanding these metabolic changes is crucial for early diagnosis and therapeutic strategies.

Purpose of the Study:

• To investigate the pathogenic linkage of PD by examining interorgan metabolic communication.
• To identify potential diagnostic biomarkers for early-stage PD.
• To explore the role of autonomic dysfunction in PD-related metabolic alterations.

Main Methods:

• Utilized Iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in 1,158 PD patients.
• Performed serum exosome miRNA transcriptome and plasma metabolome analyses in de novo PD patients and controls.
• Conducted in vitro experiments to assess thyroid hormone effects on cellular metabolism.

Main Results:

• Confirmed sympathetic denervation of the thyroid in PD patients via MIBG scintigraphy.
• Observed decreased thyroxine levels and insufficient fatty acid β-oxidation in drug-naïve PD patients.
• Identified enrichment of the peroxisome proliferator-activated receptor (PPARα) axis in PD, linking thyroid hormone to PPARα-dependent β-oxidation.

Conclusions:

• Early-stage PD is associated with disorganized interorgan communication between the thyroid and liver.
• These metabolic disruptions may serve as sensitive diagnostic biomarkers for PD.
• Findings highlight the role of metabolic dysregulation in PD pathogenesis.