ArticleJCI insight2020
Early disruption of nerve mitochondrial and myelin lipid homeostasis in obesity-induced diabetes.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- Effects of obesity on brain health and cognition.Nature reviews. Neurology · 2026Review
- Diabetes and the Metabolic Syndrome as Drivers of Neurodegeneration: Convergent Mechanisms Linking Peripheral Neuropathy and Dementia.Annals of neurology · 2026Review
- Tmem117, an oligodendrocyte-enriched regulator of NCX activity, links myelin homeostasis to counterregulation and metabolic health.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Bioenergetic failure in diabetic peripheral neuropathy: from glucotoxicity to multidimensional metabolic imbalance.Journal of neurology · 2026Review
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- Glial Triad in Diabetic Neuropathy: Central Players in Neuropathic Pain Pathogenesis and Disease-Modifying Therapeutic Avenues.Biomedicines · 2026Review
- A novel extracellular flux assay workflow uncovers impaired sciatic nerve mitochondrial respiration in diabetic db/db mice.Cell communication and signaling : CCS · 2026Article
- Exploring ceramide as a novel biomarker and therapeutic target for Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Associations Between Multidimensional Obesity Indices and Diabetic Peripheral Neuropathy and Comparison of Their Discriminative Performance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.Gut microbes · 2025Review
- Myelin dysfunction in aging and brain disorders: mechanisms and therapeutic opportunities.Molecular neurodegeneration · 2025Review
- Obesity negatively impacts corneal nerves in patients with diabetes mellitus.Eye and vision (London, England) · 2025Article
- SGK1 drives hippocampal demyelination and diabetes-associated cognitive dysfunction in mice.Nature communications · 2025Article
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.Current Alzheimer research · 2025Review
- Myelin Lipid Alterations in Neurodegenerative Diseases: Landscape and Pathogenic Implications.Antioxidants & redox signaling · 2024Review
- Ferroptosis contributes to diabetes-induced visual pathway neuronal damage via iron accumulation and GPX4 inactivation.Metabolic brain disease · 2024Article
- Quantification of lipoproteins by proton nuclear magnetic resonance spectroscopy (Journal of endocrinological investigation · 2024Article
- Glial cell alterations in diabetes-induced neurodegeneration.Cellular and molecular life sciences : CMLS · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Diabetic neuropathy is a major complication of diabetes. Current treatment options alleviate pain but do not stop the progression of the disease. At present, there are no approved disease-modifying therapies. Thus, developing more effective therapies remains a major unmet medical need. Seeking to better understand the molecular mechanisms driving peripheral neuropathy, as well as other neurological complications associated with diabetes, we performed spatiotemporal lipidomics, biochemical, ultrastructural, and physiological studies on PNS and CNS tissue from multiple diabetic preclinical models. We unraveled potentially novel molecular fingerprints underlying nerve damage in obesity-induced diabetes, including an early loss of nerve mitochondrial (cardiolipin) and myelin signature (galactosylceramide, sulfatide, and plasmalogen phosphatidylethanolamine) lipids that preceded mitochondrial, myelin, and axonal structural/functional defects; started in the PNS; and progressed to the CNS at advanced diabetic stages. Mechanistically, we provided substantial evidence indicating that these nerve mitochondrial/myelin lipid abnormalities are (surprisingly) not driven by hyperglycemia, dysinsulinemia, or insulin resistance, but rather associate with obesity/hyperlipidemia. Importantly, our findings have major clinical implications as they open the door to novel lipid-based biomarkers to diagnose and distinguish different subtypes of diabetic neuropathy (obese vs. nonobese diabetics), as well as to lipid-lowering therapeutic strategies for treatment of obesity/diabetes-associated neurological complications and for glycemic control.
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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.