PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease
Version 1
: Received: 10 April 2024 / Approved: 11 April 2024 / Online: 11 April 2024 (09:32:33 CEST)
How to cite:
Parafati, M.; La Russa, D.; Lascala, A.; Crupi, F.; Riillo, C.; Fotschki, B.; Mollace, V.; Janda, E. Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease. Preprints2024, 2024040784. https://doi.org/10.20944/preprints202404.0784.v1
Parafati, M.; La Russa, D.; Lascala, A.; Crupi, F.; Riillo, C.; Fotschki, B.; Mollace, V.; Janda, E. Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease. Preprints 2024, 2024040784. https://doi.org/10.20944/preprints202404.0784.v1
Parafati, M.; La Russa, D.; Lascala, A.; Crupi, F.; Riillo, C.; Fotschki, B.; Mollace, V.; Janda, E. Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease. Preprints2024, 2024040784. https://doi.org/10.20944/preprints202404.0784.v1
APA Style
Parafati, M., La Russa, D., Lascala, A., Crupi, F., Riillo, C., Fotschki, B., Mollace, V., & Janda, E. (2024). Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease. Preprints. https://doi.org/10.20944/preprints202404.0784.v1
Chicago/Turabian Style
Parafati, M., Vincenzo Mollace and Elzbieta Janda. 2024 "Dramatic Suppression of Lipogenesis and No Increase in Beta- Oxidation Are the Main Effects of Bergamot Flavonoids on Gene Expression in Fatty Liver Disease" Preprints. https://doi.org/10.20944/preprints202404.0784.v1
Abstract
Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of Bergamot Polyphenol Fraction (BPF). CAF diet caused a strong upregulation of the gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6). However, only one -oxidation gene (Cpt1a) and a few autophagy genes were modulated in the CAF group compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca, Fasn and Scd1, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no -oxidation gene expression changes were observed, suggesting minor transcriptional effects on autophagy. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on -oxidation, but profound suppression of de-novo lipogenesis.
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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