ArticleCell death & disease2022
Palmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- Ciliary Membrane Lipid Homeostasis in Health and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- 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
- Primary Cilia as Integrative Hubs of Metabolic Signaling in Type 2 Diabetes: Inter-Organ Evidence From Central, Peripheral, and Pancreatic Islet Tissues.Journal of cellular physiology · 2026Review
- Primary cilia dysfunction: A critical driver of metabolic diseases (Review).International journal of molecular medicine · 2026Review
- Three-dimensional approaches to measuring primary cilia in hippocampal neurons: A comparative analysis.Journal of neuropathology and experimental neurology · 2026Article
- The microbiota-gut-brain axis: novel mechanisms and therapeutic frontiers in obesity and type 2 diabetes.NPJ biofilms and microbiomes · 2026Review
- The nociceptor primary cilium.Brain : a journal of neurology · 2026Review
- Glycogen Synthase Kinase-3β Mediates Suppression of Neurite Outgrowth Through Sonic Hedgehog Signalling in Palmitic Acid-Exposed Neuro2A Cells.Molecular neurobiology · 2026Article
- Anti-cancer effect of palmitic acid against the endometrial cancer progression via inducing ferroptosis.Biochemistry and biophysics reports · 2026Article
- Identification of ACBP as a potential target in ciliopathic obesity through multi-omics network analysis.Nature communications · 2026Article
- A Novel Framework for Quantitative Analysis of Neuronal Primary Cilia in Brain Tissue.bioRxiv : the preprint server for biology · 2025Article
- Chemical Analysis and Antioxidant Activities of Resin Fractions fromMolecules (Basel, Switzerland) · 2025Article
- Palmitic Acid Accelerates Endothelial Cell Injury and Cardiovascular Dysfunction via Palmitoylation of PKM2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intravital imaging reveals glucose-dependent cilia movement in pancreatic islets in vivo.Metabolism: clinical and experimental · 2025Article
- Multiple Roles of Palmitic Acid in Cardiovascular Diseases.Journal of inflammation research · 2025Review
- Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice.Nature communications · 2024Article
- Regulation of genes involved in the metabolic adaptation of murine microglial cells in response to elevated HIF-1α mediated activation.Immunogenetics · 2024Article
- Role of lipids in the control of autophagy and primary cilium signaling in neurons.Neural regeneration research · 2024Review
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Authors and funding
25 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Palmitic acid (PA) is significantly increased in the hypothalamus of mice, when fed chronically with a high-fat diet (HFD). PA impairs insulin signaling in hypothalamic neurons, by a mechanism dependent on autophagy, a process of lysosomal-mediated degradation of cytoplasmic material. In addition, previous work shows a crosstalk between autophagy and the primary cilium (hereafter cilium), an antenna-like structure on the cell surface that acts as a signaling platform for the cell. Ciliopathies, human diseases characterized by cilia dysfunction, manifest, type 2 diabetes, among other features, suggesting a role of the cilium in insulin signaling. Cilium depletion in hypothalamic pro-opiomelanocortin (POMC) neurons triggers obesity and insulin resistance in mice, the same phenotype as mice deficient in autophagy in POMC neurons. Here we investigated the effect of chronic consumption of HFD on cilia; and our results indicate that chronic feeding with HFD reduces the percentage of cilia in hypothalamic POMC neurons. This effect may be due to an increased amount of PA, as treatment with this saturated fatty acid in vitro reduces the percentage of ciliated cells and cilia length in hypothalamic neurons. Importantly, the same effect of cilia depletion was obtained following chemical and genetic inhibition of autophagy, indicating autophagy is required for ciliogenesis. We further demonstrate a role for the cilium in insulin sensitivity, as cilium loss in hypothalamic neuronal cells disrupts insulin signaling and insulin-dependent glucose uptake, an effect that correlates with the ciliary localization of the insulin receptor (IR). Consistently, increased percentage of ciliated hypothalamic neuronal cells promotes insulin signaling, even when cells are exposed to PA. Altogether, our results indicate that, in hypothalamic neurons, impairment of autophagy, either by PA exposure, chemical or genetic manipulation, cause cilia loss that impairs insulin sensitivity.
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