ArticleThe Journal of clinical investigation2011
Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
139 citing papers in PubMed, 3 syntheses or guidelines pooled it, 205 citations in OpenAlex.
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- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Copy number variations associated with obesity-related traits in African Americans: a joint analysis between GENOA and HyperGEN.Obesity (Silver Spring, Md.) · 2012Pooled it
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- Mitophagy and Noncoding RNA Regulation in Type 2 Diabetes Mellitus: Molecular Mechanisms, Tissue-Specific Evidence and Translational Perspective.Biomedicines · 2026Review
- Skeletal muscle H3K18 lactylation inhibits hepatic gluconeogenesis through IL-6 mediated interorgan communication.Science advances · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Mitochondrial quality control in cardiomyocytes: safeguarding the heart against disease and ageing.Nature reviews. Cardiology · 2025Review
- High fat diet (HFD) induced hepatic lipogenic metabolism and lipotoxicity via Parkin-dependent mitophagy and Errα signal of Pelteobagrus fulvidraco.Journal of animal science and biotechnology · 2025Article
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- Interplay between lipid droplets and alpha-synuclein: implication in Parkinson's disease pathogenesis.Frontiers in molecular neuroscience · 2025Review
- Mechanism and regulation of mitophagy in liver diseases: a review.Frontiers in cell and developmental biology · 2025Review
- VPS28 regulates triglyceride synthesis via ubiquitination in bovine mammary epithelial cells.Scientific reports · 2024Article
- Review
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- Extreme-Phenotype Genome-Wide Association Analysis for Growth Traits in Spotted Sea Bass (Animals : an open access journal from MDPI · 2024Article
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- CD36 inhibition reduces non-small-cell lung cancer development through AKT-mTOR pathway.Cell biology and toxicology · 2024Article
- Mitophagy Responds to the Environmental Temperature and Regulates Mitochondrial Mass in Adipose Tissues.Advances in experimental medicine and biology · 2024Review
- The role of mitochondrial dynamics in disease.MedComm · 2023Review
79 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
It has long been hypothesized that abnormalities in lipid biology contribute to degenerative brain diseases. Consistent with this, emerging epidemiologic evidence links lipid alterations with Parkinson disease (PD), and disruption of lipid metabolism has been found to predispose to α-synuclein toxicity. We therefore investigated whether Parkin, an E3 ubiquitin ligase found to be defective in patients with early onset PD, regulates systemic lipid metabolism. We perturbed lipid levels by exposing Parkin+/+ and Parkin-/- mice to a high-fat and -cholesterol diet (HFD). Parkin-/- mice resisted weight gain, steatohepatitis, and insulin resistance. In wild-type mice, the HFD markedly increased hepatic Parkin levels in parallel with lipid transport proteins, including CD36, Sr-B1, and FABP. These lipid transport proteins were not induced in Parkin-/- mice. The role of Parkin in fat uptake was confirmed by increased oleate accumulation in hepatocytes overexpressing Parkin and decreased uptake in Parkin-/- mouse embryonic fibroblasts and patient cells harboring complex heterozygous mutations in the Parkin-encoding gene PARK2. Parkin conferred this effect, in part, via ubiquitin-mediated stabilization of the lipid transporter CD36. Reconstitution of Parkin restored hepatic fat uptake and CD36 levels in Parkin-/- mice, and Parkin augmented fat accumulation during adipocyte differentiation. These results demonstrate that Parkin is regulated in a lipid-dependent manner and modulates systemic fat uptake via ubiquitin ligase-dependent effects. Whether this metabolic regulation contributes to premature Parkinsonism warrants investigation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.