Mexican Ganoderma Lucidum Extracts Decrease Lipogenesis Modulating Transcriptional Metabolic Networks and Gut Microbiota in C57BL/6 Mice Fed with a High-Cholesterol Diet

• Published in: Nutrients 2020-12, Vol.13 (1), p.38
• Main Authors: Romero-Córdoba, Sandra L, Salido-Guadarrama, Ivan, Meneses, María E, Cosentino, Giulia, Iorio, Marilena V, Tagliabue, Elda, Torres, Nimbe, Sánchez-Tapia, Mónica, Bonilla, Myrna, Castillo, Ivan, Petlacalco, Beatriz, Tovar, Armando R, Martínez-Carrera, Daniel
• Format: Article
• Language: English
• Subjects: Acetylsalicylic acid; Animals; Anticholesteremic Agents - administration & dosage; Antidiabetics; Basidiocarps; Biosynthesis; Cholesterol; Cholesterol, Dietary - administration & dosage; Diabetes mellitus; Diet; Enrichment; Gastrointestinal Microbiome - physiology; Gene expression; Genes; High cholesterol diet; Hypercholesterolemia; Hyperlipidemia; Intestinal microflora; Kidney - metabolism; Lipid Metabolism - drug effects; Lipid Metabolism - genetics; Lipids; Lipogenesis; Lipogenesis - drug effects; Lipogenesis - genetics; Liver; Liver - metabolism; Macrophages; Male; Metabolic disorders; Metabolic networks; Metabolic Networks and Pathways - drug effects; Metabolic Networks and Pathways - genetics; Metabolic pathways; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; Microbiota; Mushrooms; Natural products; Prebiotics; Prebiotics - administration & dosage; RAW 264.7 Cells; Reishi - chemistry; Simvastatin; Substrates; Transcription; Transcriptome - drug effects; Transcriptome - physiology
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13010038

Prevention of hyperlipidemia and associated diseases is a health priority. Natural products, such as the medicinal mushroom ( ), have demonstrated hypocholesterolemic, prebiotic and antidiabetic properties. However, the underlying transcriptomic mechanisms by which exerts bioactivities are not completely understood. We report a comprehensive hepatic and renal transcriptome profiling of C57BL/6 mice under the consumption of a high-cholesterol diet and two standardized extracts obtained from basidiocarps cultivated on conventional substrate ( -1) or substrate containing acetylsalicylic acid (ASA; -2). We showed that extracts modulate relevant metabolic pathways involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. The -2 extract exerts a major modulation over gene expression programs showing the highest similarity with simvastatin druggable-target-genes and these are enriched more in processes related to human obesity alterations in the liver. We further show a subset of -modulated genes correlated with enrichment and the reduction of circulating cholesterol-derived fats. Moreover, extracts induce a significant decrease of macrophage lipid storage, which occurs concomitantly with the down-modulation of Fasn and Elovl6. Collectively, this evidence suggests a new link between hypocholesterolemic and prebiotic activity, revealing thereby that standardized Mexican extracts are a novel transcriptome modulator to prevent metabolic disorders associated with hypercholesterolemia.