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

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.