ArticleAntioxidants (Basel, Switzerland)2022
Empagliflozin-Enhanced Antioxidant Defense Attenuates Lipotoxicity and Protects Hepatocytes by Promoting FoxO3a- and Nrf2-Mediated Nuclear Translocation via the CAMKK2/AMPK Pathway.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Palmitic Acid-Induced Hepatotoxicity in Adult Zebrafish: Molecular Mechanisms and Advances in Intervention.Biology · 2026Review
- Targeted metabolomics to assess positive effects of empagliflozin in a Parkinson's disease model: focused on the kynurenine pathway and oxidative stress.Scientific reports · 2026Article
- Hepatocyte PIEZO1 Negatively Regulates Lipogenesis and Ameliorates MASLD by Sensing Membrane Tension and Activating AMPK.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Silencing of telomerase RNA component induces autophagy and ferroptosis in A549 and H838 lung cancer cells via AMPK-mediated signaling.Molecular and cellular biochemistry · 2026Article
- Mitochondrial ROS dyshomeostasis: a key driver of accelerated supraspinatus atrophy after rotator cuff injury.Frontiers in physiology · 2026Review
- Mechanism of Sodium-Glucose Cotransporter-2 Inhibitors for Uricosuria.Electrolyte & blood pressure : E & BP · 2025Review
- Empagliflozin mitigates doxorubicin-induced hepatotoxicity by reducing inflammation, oxidative stress, and apoptosis in male NMRI mice.Medical oncology (Northwood, London, England) · 2025Article
- 5-HT regulates resistance to aumolertinib by attenuating ferroptosis in lung adenocarcinoma.EMBO molecular medicine · 2025Article
- The Combination Empagliflozin/Metformin Attenuates the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Diet-Induced Experimental Rat Model.International journal of molecular sciences · 2025Article
- Mechanistic and Molecular Insights into Empagliflozin's Role in Ferroptosis and Inflammation Trajectories in Acetaminophen-Induced Hepatotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Multi-dimensional roles of sodium-glucose cotransporter 2 inhibitors: beyond hypoglycemic and cardiorenal protection.Frontiers in endocrinology · 2025Review
- SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts.The Journal of clinical investigation · 2024Article
- Artemisinin conferred cytoprotection to human retinal pigment epithelial cells exposed to amiodarone-induced oxidative insult by activating the CaMKK2/AMPK/Nrf2 pathway.Journal of translational medicine · 2024Article
- Extracellular Superoxide Dismutase Attenuates Hepatic Oxidative Stress in Nonalcoholic Fatty Liver Disease through the Adenosine Monophosphate-Activated Protein Kinase Activation.Antioxidants (Basel, Switzerland) · 2023Article
- Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy.International journal of molecular sciences · 2023Article
- Canagliflozin Delays Aging of HUVECs Induced by Palmitic Acid via the ROS/p38/JNK Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Canagliflozin Attenuates Lipotoxicity in Cardiomyocytes by Inhibiting Inflammation and Ferroptosis through Activating AMPK Pathway.International journal of molecular sciences · 2023Article
- OL-FS13 Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting miR-21-3p Expression.Current neuropharmacology · 2023Article
- Interplay between metabolic dysfunction-associated fatty liver disease and chronic kidney disease: Epidemiology, pathophysiologic mechanisms, and treatment considerations.World journal of gastroenterology · 2022Review
- Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Lipotoxicity is an important factor in the development and progression of nonalcoholic steatohepatitis. Excessive accumulation of saturated fatty acids can increase the substrates of the mitochondrial electron transport chain in hepatocytes and cause the generation of reactive oxygen species, resulting in oxidative stress, mitochondrial dysfunction, loss of mitochondrial membrane potential, impaired triphosphate (ATP) production, and fracture and fragmentation of mitochondria, which ultimately leads to hepatocellular inflammatory injuries, apoptosis, and necrosis. In this study, we systematically investigated the effects and molecular mechanisms of empagliflozin on lipotoxicity in palmitic acid-treated LO2 cell lines. We found that empagliflozin protected hepatocytes and inhibited palmitic acid-induced lipotoxicity by reducing oxidative stress, improving mitochondrial functions, and attenuating apoptosis and inflammation responses. The mechanistic study indicated that empagliflozin significantly activated adenosine 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα) through Calcium/Calmodulin dependent protein kinase kinase beta (CAMKK2) instead of liver kinase B1 (LKB1) or TGF-beta activated kinase (TAK1). The activation of empagliflozin on AMPKα not only promoted FoxO3a phosphorylation and thus forkhead box O 3a (FoxO3a) nuclear translocation, but also promoted Nrf2 nuclear translocation. Furthermore, empagliflozin significantly upregulated the expressions of antioxidant enzymes superoxide dismutase (SOD) and HO-1. In addition, empagliflozin did not attenuate lipid accumulation at all. These results indicated that empagliflozin mitigated lipotoxicity in saturated fatty acid-induced hepatocytes, likely by promoting antioxidant defense instead of attenuating lipid accumulation through enhanced FoxO3a and Nrf2 nuclear translocation dependent on the CAMKK2/AMPKα pathway. The CAMKK2/AMPKα pathway might serve as a promising target in treatment of lipotoxicity in nonalcoholic steatohepatitis.
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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.