ArticleThe Journal of clinical investigation2013
Leptin regulation of Hsp60 impacts hypothalamic insulin signaling.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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.
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Who cites it
70 citing papers in PubMed, 133 citations in OpenAlex.
- Exercise elicits mitonuclear protein imbalance and UPRJournal of physiology and biochemistry · 2026Article
- HSPD1 regulates angiotensin II‑induced atrial fibrillation via the PPAR signaling pathway.Molecular medicine reports · 2025Article
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- Altered mitochondrial unfolded protein response and FGF21 secretion in MASLD progression and the effect of exercise intervention.Scientific reports · 2025Article
- UPRmt-regulated mitokines: novel strategies for myocardial injury repair.Frontiers in cell and developmental biology · 2025Review
- Targeting Mitochondrial Dysfunction for the Prevention and Treatment of Metabolic Disease by Bioactive Food Components.Journal of lipid and atherosclerosis · 2024Review
- Biliverdin Reductase-A integrates insulin signaling with mitochondrial metabolism through phosphorylation of GSK3β.Redox biology · 2024Article
- Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.International journal of molecular sciences · 2024Review
- PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3β and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma.Cell death & disease · 2024Article
- Mitochondrial Unfolded Protein Response GeneInternational journal of molecular sciences · 2024Article
- Aberrant mitochondrial aggregation of TDP-43 activated mitochondrial unfolded protein response and contributed to recovery of acetaminophen induced acute liver injury.Toxicology research · 2024Article
- Mitochondrial Quality Control via Mitochondrial Unfolded Protein Response (mtUPR) in Ageing and Neurodegenerative Diseases.Biomolecules · 2023Review
- CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.Nature communications · 2023Article
- Exploring the Role of Hsp60 in Alzheimer's Disease and Type 2 Diabetes: Suggestion for Common Drug Targeting.International journal of molecular sciences · 2023Review
- Loss of insulin signaling in astrocytes exacerbates Alzheimer-like phenotypes in a 5xFAD mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Chaperonin counteracts diet-induced non-alcoholic fatty liver disease by aiding sirtuin 3 in the control of fatty acid oxidation.Diabetologia · 2023Article
- The Role of Heat Shock Proteins in the Pathogenesis of Polycystic Ovarian Syndrome: A Review of the Literature.International journal of molecular sciences · 2023Review
- mtUPR Modulation as a Therapeutic Target for Primary and Secondary Mitochondrial Diseases.International journal of molecular sciences · 2023Review
- Article
- Leptin signaling and leptin resistance.Medical review (2021) · 2022Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes is characterized by insulin resistance and mitochondrial dysfunction in classical target tissues such as muscle, fat, and liver. Using a murine model of type 2 diabetes, we show that there is hypothalamic insulin resistance and mitochondrial dysfunction due to downregulation of the mitochondrial chaperone HSP60. HSP60 reduction in obese, diabetic mice was due to a lack of proper leptin signaling and was restored by leptin treatment. Knockdown of Hsp60 in a mouse hypothalamic cell line mimicked the mitochondrial dysfunction observed in diabetic mice and resulted in increased ROS production and insulin resistance, a phenotype that was reversed with antioxidant treatment. Mice with a heterozygous deletion of Hsp60 exhibited mitochondrial dysfunction and hypothalamic insulin resistance. Targeted acute downregulation of Hsp60 in the hypothalamus also induced insulin resistance, indicating that mitochondrial dysfunction can cause insulin resistance in the hypothalamus. Importantly, type 2 diabetic patients exhibited decreased expression of HSP60 in the brain, indicating that this mechanism is relevant to human disease. These data indicate that leptin plays an important role in mitochondrial function and insulin sensitivity in the hypothalamus by regulating HSP60. Moreover, leptin/insulin crosstalk in the hypothalamus impacts energy homeostasis in obesity and insulin-resistant states.
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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.