ArticleThe Journal of biological chemistry2016
Sirtuin 3 (SIRT3) Regulates α-Smooth Muscle Actin (α-SMA) Production through the Succinate Dehydrogenase-G Protein-coupled Receptor 91 (GPR91) Pathway in Hepatic Stellate Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 63 citations in OpenAlex.
- Gemigliptin Alleviates Succinate Induced Endoplasmic Reticulum Stress and Activation of Hepatic Stellate Cells.Journal of Korean medical science · 2025Article
- The Role of Mitochondrial Complexes in Liver Diseases.Journal of clinical and translational hepatology · 2025Review
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Silybin inhibits succinate production and secretion in hepatocytes to reverse liver fibrosis.Archives of pharmacal research · 2025Article
- From inflammation to healing: the crucial role of GPR91 activation and SDH inhibition in chronic diabetic wound recovery.Stem cell research & therapy · 2025Article
- SIRT3, a New Hope in Liver Diseases from Pathogenic Mechanisms to Therapeutic Strategies.Current pharmaceutical biotechnology · 2025Review
- Type 2 diabetes and succinate: unmasking an age-old molecule.Diabetologia · 2024Review
- Extracellular Succinate: A Physiological Messenger and a Pathological Trigger.International journal of molecular sciences · 2023Review
- Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.Cardiovascular research · 2023Article
- Role of SIRT3 in neurological diseases and rehabilitation training.Metabolic brain disease · 2023Review
- Why Is Longevity Still a Scientific Mystery? Sirtuins-Past, Present and Future.International journal of molecular sciences · 2022Review
- Fibrogenic Pathways in Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD).International journal of molecular sciences · 2022Review
- Therapeutic Effects of Resveratrol on Nonalcoholic Fatty Liver Disease Through Inflammatory, Oxidative Stress, Metabolic, and Epigenetic Modifications.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Western Diet Decreases the Liver Mitochondrial Oxidative Flux of Succinate: Insight from a Murine NAFLD Model.International journal of molecular sciences · 2021Article
- UCP1 governs liver extracellular succinate and inflammatory pathogenesis.Nature metabolism · 2021Review
- Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite.Frontiers in pharmacology · 2021Review
- Wild Bitter Melon Extract Regulates LPS-Induced Hepatic Stellate Cell Activation, Inflammation, Endoplasmic Reticulum Stress, and Ferroptosis.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts.Frontiers in molecular biosciences · 2021Review
- Role of phosphatidylinositol 3-kinase signaling pathway in radiation-induced liver injury.The Kaohsiung journal of medical sciences · 2020Article
- Review
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuin 3 (SIRT3) is an NAD(+)-dependent protein deacetylase. Recent studies have shown that SIRT3 expression is decreased in nonalcoholic fatty liver disease (NAFLD). Moreover, SIRT3 is a key regulator of succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate. Increased succinate concentrations and the specific G protein-coupled receptor 91 (GPR91) are involved in the activation of hepatic stellate cells (HSCs). In this study, we aimed to establish whether SIRT3 regulated the SDH activity, succinate, and GPR91 expression in HSCs and an animal model of NAFLD. Our goal was also to determine whether succinate released from hepatocytes regulated HSC activation. Inhibiting SIRT3 using SIRT3 siRNA exacerbated HSC activation via the SDH-succinate-GPR91 pathway, and SIRT3 overexpression or honokiol treatment attenuated HSC activation in vitro In isolated liver and HSCs from methionine- and choline-deficient (MCD) diet-induced NAFLD, the expression of SIRT3 and SDH activity was decreased, and the succinate concentrations and GPR91 expression were increased. Moreover, we found that GPR91 knockdown or resveratrol treatment improved the steatosis in MCD diet-fed mice. This investigation revealed a novel mechanism of the SIRT3-SDH-GPR91 cascade in MCD diet-induced HSC activation in NAFLD. These findings highlight the biological significance of novel strategies aimed at targeting SIRT3 and GPR91 in HSCs with the goal of improving NAFLD treatment.
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