ArticleBiomolecules2021
The Influence of Coumestrol on Sphingolipid Signaling Pathway and Insulin Resistance Development in Primary Rat Hepatocytes.
Article in Biomolecules, 2021. 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.
- Review
- Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Comprehensive analysis of TMEM9 in human tumors.Discover oncology · 2025Article
- Postoperative insulin resistance and the intestinal microbiota: mechanisms and research advances.Microbiome research reports · 2025Review
- Exploring the anti-aging potential of phytoestrogens: focus on molecular mechanisms and menopausal symptom modulation.Frontiers in nutrition · 2025Review
- Colonic Microbiota Improves Fiber Digestion Ability and Enhances Absorption of Short-Chain Fatty Acids in Local Pigs of Hainan.Microorganisms · 2024Article
- Exploring the Therapeutic Potential of Royal Jelly in Metabolic Disorders and Gastrointestinal Diseases.Nutrients · 2024Review
- Integrated analysis of gut microbiome and its metabolites in ACE2-knockout and ACE2-overexpressed mice.Frontiers in cellular and infection microbiology · 2024Article
- How Does CBG Administration Affect Sphingolipid Deposition in the Liver of Insulin-Resistant Rats?Nutrients · 2023Article
- Protective Effects of Coumestrol on Metabolic Dysfunction and Its Estrogen Receptor-Mediated Action in Ovariectomized Mice.Nutrients · 2023Article
- Phytoestrogens and Health Effects.Nutrients · 2023Review
- Systems biology andHeliyon · 2022Article
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate.International journal of molecular sciences · 2022Review
- The Endocannabinoid System and Physical Activity-A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders.International journal of molecular sciences · 2022Review
- Lipid metabolism contribute to the pathogenesis of IgA Vasculitis.Diagnostic pathology · 2022Article
- ANGPTL8/Betatrophin Improves Glucose Tolerance in Older Mice and Metabolomic Analysis Reveals Its Role in Insulin Resistance in HepG2 Cells.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
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Authors and funding
8 authors.
Funding
Abstract
Coumestrol is a phytoestrogen widely known for its anti-diabetic, anti-oxidant, and anti-inflammatory properties. Thus, it gets a lot of attention as a potential agent in the nutritional therapy of diseases such as obesity and type 2 diabetes. In our study, we evaluated whether coumestrol affects insulin resistance development via the sphingolipid signaling pathway in primary rat hepatocytes. The cells were isolated from the male Wistar rat's liver with the use of collagenase perfusion. Next, we incubated the cells with the presence or absence of palmitic acid and/or coumestrol. Additionally, some groups were incubated with insulin. The sphingolipid concentrations were assessed by HPLC whereas the expression of all the proteins was evaluated by Western blot. Coumestrol markedly reduced the accumulation of sphingolipids, namely, ceramide and sphinganine through noticeable inhibition of the ceramide de novo synthesis pathway in insulin-resistant hepatocytes. Moreover, coumestrol augmented the expression of fatty acid transport proteins, especially FATP5 and FAT/CD36, which also were responsible for excessive sphingolipid accumulation. Furthermore, coumestrol altered the sphingolipid salvage pathway, which was observed as the excessive deposition of the sphingosine-1-phosphate and sphingosine. Our study clearly showed that coumestrol ameliorated hepatic insulin resistance in primary rat hepatocytes. Thus, we believe that our study may contribute to the discovery of novel preventive and therapeutic methods for metabolic disorders.
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