Scope: Type 2 diabetes and nonalcoholic fatty liver diseases (NAFLDs) are promoted by insulin resistance (IR), which alters lipid homeostasis in the liver. This study aims to investigate the effect of N-methylpyridinium (NMP), a bioactive alkaloid of coffee brew, on lipid metabolism in hepatocytes. Methods and results: The effect of NMP in modulating lipid metabolism is evaluated at physiological concentrations in a diabetes cell model represented by HepG2 cells cultured in a high-glucose medium. Hyperglycemia triggers lipid droplet accumulation in cells and enhances the lipogenic gene expression, which is transactivated by sterol regulatory element binding protein-1 (SREBP-1). Lipid droplet accumulation alters the redox status and endoplasmic reticulum (ER) stress, leading to the activation of the unfolded protein response and antioxidative pathways by X-Box Binding Protein 1(XBP-1)/eukaryotic Initiation Factor 2 alpha (eIF2α) Protein Kinase RNA-Like ER Kinase and nuclear factor erythroid 2-related factor 2 (NRF2), respectively. NMP induces the phosphorylation of AMP-dependent protein kinase (AMPK) and acetyl-CoA carboxylase α (ACACA), and improves the redox status and ER homeostasis, essential steps to reduce lipogenesis and lipid droplet accumulation. Conclusion: These results suggest that NMP may be beneficial for the management of T2D and NAFLD by ameliorating the cell oxidative and ER homeostasis and lipid metabolism.

Coffee Bioactive N-Methylpyridinium: Unveiling Its Antilipogenic Effects by Targeting De Novo Lipogenesis in Human Hepatocytes / Giannotti, L.; Stanca, E.; Di Chiara Stanca, B.; Spedicato, F.; Massaro, M.; Quarta, S.; Del Rio, D.; Mena, P.; Siculella, L.; Damiano, F.. - In: MOLECULAR NUTRITION & FOOD RESEARCH. - ISSN 1613-4125. - 68:21(2024). [10.1002/mnfr.202400338]

Coffee Bioactive N-Methylpyridinium: Unveiling Its Antilipogenic Effects by Targeting De Novo Lipogenesis in Human Hepatocytes

Spedicato F.;Del Rio D.;Mena P.;
2024-01-01

Abstract

Scope: Type 2 diabetes and nonalcoholic fatty liver diseases (NAFLDs) are promoted by insulin resistance (IR), which alters lipid homeostasis in the liver. This study aims to investigate the effect of N-methylpyridinium (NMP), a bioactive alkaloid of coffee brew, on lipid metabolism in hepatocytes. Methods and results: The effect of NMP in modulating lipid metabolism is evaluated at physiological concentrations in a diabetes cell model represented by HepG2 cells cultured in a high-glucose medium. Hyperglycemia triggers lipid droplet accumulation in cells and enhances the lipogenic gene expression, which is transactivated by sterol regulatory element binding protein-1 (SREBP-1). Lipid droplet accumulation alters the redox status and endoplasmic reticulum (ER) stress, leading to the activation of the unfolded protein response and antioxidative pathways by X-Box Binding Protein 1(XBP-1)/eukaryotic Initiation Factor 2 alpha (eIF2α) Protein Kinase RNA-Like ER Kinase and nuclear factor erythroid 2-related factor 2 (NRF2), respectively. NMP induces the phosphorylation of AMP-dependent protein kinase (AMPK) and acetyl-CoA carboxylase α (ACACA), and improves the redox status and ER homeostasis, essential steps to reduce lipogenesis and lipid droplet accumulation. Conclusion: These results suggest that NMP may be beneficial for the management of T2D and NAFLD by ameliorating the cell oxidative and ER homeostasis and lipid metabolism.
2024
Coffee Bioactive N-Methylpyridinium: Unveiling Its Antilipogenic Effects by Targeting De Novo Lipogenesis in Human Hepatocytes / Giannotti, L.; Stanca, E.; Di Chiara Stanca, B.; Spedicato, F.; Massaro, M.; Quarta, S.; Del Rio, D.; Mena, P.; Siculella, L.; Damiano, F.. - In: MOLECULAR NUTRITION & FOOD RESEARCH. - ISSN 1613-4125. - 68:21(2024). [10.1002/mnfr.202400338]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/3014595
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