ArticleMolecular & cellular oncology2020
Palmitic acid reduces the autophagic flux in hypothalamic neurons by impairing autophagosome-lysosome fusion and endolysosomal dynamics.
Article in Molecular & cellular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Autophagy in hypothalamic POMC and AgRP neurons: mechanisms and therapeutic implications for obesity.International journal of obesity (2005) · 2026Review
- Cortical-Hypothalamic Assembloids Uncover the Cortical Regulation of Hypothalamic Responses to Fatty Acid.Cell proliferation · 2026Article
- Docosahexaenoic Acid Protects Schwann Cells Against Palmitic Acid-Induced Lipotoxicity by Modulating Autophagy, ER Stress, and Lipid Handling.Neurochemical research · 2026Article
- Palmitic acid-induced autolysosomal dysfunction and lipotoxicity in neuroinflammation and neurodegeneration.Neural regeneration research · 2026Article
- Article
- Restoration of lysosomal membrane integrity in cell models of Pompe disease depends on fatty acid synthase and its product palmitic acid.Cellular & molecular biology letters · 2026Article
- p38 mitogen-activated protein kinase drives senescence in CD4Immunity & ageing : I & A · 2025Article
- Autolysosomal Dysfunction in Obesity-induced Metabolic Inflammation and Related Disorders.Current obesity reports · 2025Review
- AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.Autophagy · 2025Article
- Multiple Roles of Palmitic Acid in Cardiovascular Diseases.Journal of inflammation research · 2025Review
- Article
- Organelle-Targeted Laurdans Measure Heterogeneity in Subcellular Membranes and Their Responses to Saturated Lipid Stress.ACS chemical biology · 2024Article
- Role of lipids in the control of autophagy and primary cilium signaling in neurons.Neural regeneration research · 2024Review
- Sex differences in response to obesity and caloric restriction on cognition and hippocampal measures of autophagic-lysosomal transcripts and signaling pathways.BMC neuroscience · 2024Article
- Impaired hepatic autophagy exacerbates hepatotoxin induced liver injury.Cell death discovery · 2023Article
- Neuronal primary cilia integrate peripheral signals with metabolic drives.Frontiers in physiology · 2023Review
- Rethinking of Alzheimer's disease: Lysosomal overloading and dietary therapy.Frontiers in aging neuroscience · 2023Article
- Paraoxonase-2 contributes to promoting lipid metabolism and mitochondrial function via autophagy activation.Scientific reports · 2022Article
- Palmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism.Cell death & disease · 2022Article
- Free fatty acid treatment of mouse preimplantation embryos demonstrates contrasting effects of palmitic acid and oleic acid on autophagy.American journal of physiology. Cell physiology · 2022Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-fat diet (HFD)-induced obesity is associated with increased cancer risk. Long-term feeding with HFD increases the concentration of the saturated fatty acid palmitic acid (PA) in the hypothalamus. We previously showed that, in hypothalamic neuronal cells, exposure to PA inhibits the autophagic flux, which is the whole autophagic process from the synthesis of the autophagosomes, up to their lysosomal fusion and degradation. However, the mechanism by which PA impairs autophagy in hypothalamic neurons remains unknown. Here, we show that PA-mediated reduction of the autophagic flux is not caused by lysosomal dysfunction, as PA treatment does not impair lysosomal pH or the activity of cathepsin B.Instead, PA dysregulates autophagy by reducing autophagosome-lysosome fusion, which correlates with the swelling of endolysosomal compartments that show areduction in their dynamics. Finally, because lysosomes undergo constant dynamic regulation by the small Rab7 GTPase, we investigated the effect of PA treatment on its activity. Interestingly, we found PA treatment altered the activity of Rab7. Altogether, these results unveil the cellular process by which PA exposure impairs the autophagic flux. As impaired autophagy in hypothalamic neurons promotes obesity, and balanced autophagy is required to inhibit malignant transformation, this could affect tumor initiation, progression, and/or response to therapy of obesity-related cancers.
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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 Socratic graph.