ArticleInternational journal of molecular sciences2022
Sirt3 Pharmacologically Promotes Insulin Sensitivity through PI3/AKT/mTOR and Their Downstream Pathway in Adipocytes.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Targeted activation of PPARG or AKT1 alleviates liver injury in mice with type 2 diabetes and sepsis by modulating inflammatory and metabolic pathways.Annals of medicine · 2026Article
- Jionoside B1 Sensitizes TNBC to Cisplatin by Inhibiting SIRT3-Mediated Oxidative Stress Defense.Biomedicines · 2026Article
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Sirtuin 3 in diabetic kidney disease: mechanisms and pharmacotherapy.Renal failure · 2025Review
- 7,8-dihydroxyflavone attenuates NIH IIIA subtype chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) via TrkB/AKT/SIRT3 signaling activation.Translational andrology and urology · 2025Article
- Mechanisms of gypenosides in type 2 diabetes mellitus via regulation of m6A methylase METTL3/14 and demethylase FTO.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Targeting FABP4 to Inhibit AGEs-RAGE/NF-κB Signalling Effectively Ameliorates Nucleus Pulposus Dysfunction and Angiogenesis in Obesity-Related Intervertebral Disc Degeneration.Cell proliferation · 2025Article
- The mTOR signaling pathway mediates the phenotypic switch between adipocytes and osteocytes in mice with obesity-related osteoporosis.European journal of medical research · 2025Article
- Adipocyte-expressed SIRT3 manipulates carnitine pool to orchestrate metabolic reprogramming and polarization of macrophages.Cell death & disease · 2025Article
- Article
- mTOR Dysregulation, Insulin Resistance, and Hypertension.Biomedicines · 2024Review
- Honokiol relieves hippocampal neuronal damage in Alzheimer's disease by activating the SIRT3-mediated mitochondrial autophagy.CNS neuroscience & therapeutics · 2024Article
- Honokiol Mitigates Metabolic-Associated Fatty Liver Disease by Regulating Nrf2 and RIPK3 Signaling Pathways.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- SIRT3/GLUT4 signaling activation by metformin protect against cisplatin-induced ototoxicity in vitro.Archives of toxicology · 2023Article
- Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)-Searching for Epigenetic Factors.International journal of molecular sciences · 2022Review
- Virtual Screening in the Identification of Sirtuins' Activity Modulators.Molecules (Basel, Switzerland) · 2022Review
- SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Sirtuin-3 (Sirt3) is a major mitochondrial deacetylase enzyme that regulates multiple metabolic pathways, and its expression is decreased in diabetes type 1 and type 2 diabetes. This study aimed to elucidate Sirt3's molecular mechanism in regulating insulin sensitivity in adipocytes that can contribute to the effort of targeting Sirt3 for the treatment of obesity and type 2 diabetes. We found that the Sirt3 activator honokiol (HNK) induced adipogenesis compared to the control, in contrast to Sirt3 inhibitor, 3-TYP. Accordingly, HNK increased expression of adipocyte gene markers, gene-involved lipolysis and glucose transport (GLUT4), while 3-TYP reduced expression of those genes. Interestingly, 3-TYP caused an increase in gene expression of adipocyte-specific cytokines including IL6, resistin, and TNF-α. However, changes in adipocyte-specific cytokines in HNK treated cells were not significant. In addition, HNK stimulated insulin pathway by promoting insulin receptor beta (IRβ) and PI3K/AKT/mTOR pathways, resulting in an increase in phosphorylation of the forkhead family FoxO1/FoxO3a/FoxO4 and glycogen synthase kinase-3 (GSK-3β), opposing 3-TYP. In line with these findings, HNK increased free fatty acid and glucose uptake, contrary to 3-TYP. In conclusion, Sirt3 activator-HNK induced adipogenesis and lipolysis reduced adipocytes specific cytokines. Intriguingly, HNK activated insulin signaling pathway and increased free fatty acid as well as glucose uptake and transport, in sharp contrast to 3-TYP. These results indicate that, via insulin signaling regulation, Sirt3 activation by HNK improves insulin resistance, while Sirt3 inhibition by 3-TYP might precipitate insulin resistance.
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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.