{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:37:08Z","timestamp":1789591028515,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T00:00:00Z","timestamp":1728172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>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 <jats:italic>N<\/jats:italic>\u2010methylpyridinium (NMP), a bioactive alkaloid of coffee brew, on lipid metabolism in hepatocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>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\u2010glucose medium. Hyperglycemia triggers lipid droplet accumulation in cells and enhances the lipogenic gene expression, which is transactivated by sterol regulatory element binding protein\u20101 (SREBP\u20101). 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\u2010Box Binding Protein 1(XBP\u20101)\/eukaryotic Initiation Factor 2 alpha (eIF2\u03b1) Protein Kinase RNA\u2010Like ER Kinase and nuclear factor erythroid 2\u2010related factor 2 (NRF2), respectively. NMP induces the phosphorylation of AMP\u2010dependent protein kinase (AMPK) and acetyl\u2010CoA carboxylase \u03b1 (ACACA), and improves the redox status and ER homeostasis, essential steps to reduce lipogenesis and lipid droplet accumulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202400338","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T03:59:46Z","timestamp":1728273586000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Coffee Bioactive <i>N<\/i>\u2010Methylpyridinium: Unveiling Its Antilipogenic Effects by Targeting De Novo Lipogenesis in Human 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