ArticleNature communications2014
Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 181 citations in OpenAlex.
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- Crosstalk between Epigenetics and Autophagy in Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of obesity & metabolic syndrome · 2025Review
- Aspirin Attenuates Liver Fibrosis via Autophagy Induction.Journal of cellular and molecular medicine · 2025Article
- Nanoparticle-based therapeutic strategies for chronic liver diseases: Advances and insights.Liver research (Beijing, China) · 2025Review
- AMPK protects proximal tubular epithelial cells from lysosomal dysfunction and dedifferentiation induced by lipotoxicity.Autophagy · 2025Article
- Hepatocyte-Targeted Epicatechin Nanoparticles Promote Autophagy and Enhance Mitochondrial Function in Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of nanomedicine · 2025Article
- Mechanisms and therapeutic implications of selective autophagy in nonalcoholic fatty liver disease.Journal of advanced research · 2025Review
- DNA sensors in metabolic and cardiovascular diseases: Molecular mechanisms and therapeutic prospects.Immunological reviews · 2025Review
- Autophagy modulators in type 2 diabetes: A new perspective.Journal of diabetes · 2024Review
- Relationship Between Dietary Nutrient Intake and Autophagy-Related Genes in Obese Humans: A Narrative Review.Nutrients · 2024Review
- Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.Molecular metabolism · 2024Article
- Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease.Autophagy · 2024Review
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024Review
- Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD.npj metabolic health and disease · 2024Review
- Phosphoinositides and intracellular calcium signaling: novel insights into phosphoinositides and calcium coupling as negative regulators of cellular signaling.Experimental & molecular medicine · 2023Review
- The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy.Nature communications · 2023Article
- L-type calcium channel antagonist isradipine age-dependently decreases plaque associated dystrophic neurites in 5XFAD mouse model.Neuropharmacology · 2023Article
- Review
- Impaired hepatic autophagy exacerbates hepatotoxin induced liver injury.Cell death discovery · 2023Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Autophagy deregulation during obesity contributes to the pathogenesis of diverse metabolic disorders. However, without understanding the molecular mechanism of obesity interference in autophagy, development of therapeutic strategies for correcting such defects in obese individuals is challenging. Here we show that a chronic increase of the cytosolic calcium concentration in hepatocytes during obesity and lipotoxicity attenuates autophagic flux by preventing the fusion between autophagosomes and lysosomes. As a pharmacological approach to restore cytosolic calcium homeostasis in vivo, we administered the clinically approved calcium channel blocker verapamil to obese mice. Such treatment successfully increases autophagosome-lysosome fusion in liver, preventing accumulation of protein inclusions and lipid droplets and suppressing inflammation and insulin resistance. As calcium channel blockers have been safely used in clinics for the treatment of hypertension for more than 30 years, our results suggest they may be a safe therapeutic option for restoring autophagic flux and treating metabolic pathologies in obese patients.
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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.