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

Abstract

Prevention of hyperlipidemia and associated diseases is a health priority. Natural products, such as the medicinal mushroom Ganoderma lucidum (Gl), have demonstrated hypocholesterolemic, prebiotic and antidiabetic properties. However, the underlying transcriptomic mechanisms by which Gl 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 Gl extracts obtained from basidiocarps cultivated on conventional substrate (Gl-1) or substrate containing acetylsalicylic acid (ASA; Gl-2). We showed that Gl extracts modulate relevant metabolic pathways involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. The Gl-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 Gl-modulated genes correlated with Lactobacillus enrichment and the reduction of circulating cholesterol-derived fats. Moreover, Gl 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 Gl hypocholesterolemic and prebiotic activity, revealing thereby that standardized Mexican Gl extracts are a novel transcriptome modulator to prevent metabolic disorders associated with hypercholesterolemia.

Polysaccharide CM1 from Cordyceps militaris hinders adipocyte differentiation and alleviates hyperlipidemia in LDLR(+/−) hamsters

“…(4), given the big molecular weight of the polysaccharide CM1, its action both in vitro and in vivo is an interesting topic to be studied in the future. One possible mechanism by which CM1 or its physiologically degraded products modulate these genes or proteins in different organs might be by affecting gut microbiota and the metabolites, that have been demonstrated to be associated with cardiovascular diseases [ 55 , 56 ]. Future research is needed to clarify what effect CM1 has on gut microbiota, and how other potential effects contribute to CM1-mediated lipid homeostasis.…”

From Past to Present: Biotechnology in Mexico Using Algae and Fungi

“…This observation is probably based on the fact that the extracts were previously reported to exert prebiotic effects on certain gut bacteria [86]. Overall, Mexican extracts from G. lucidum offer interesting perspectives to reduce the risk of hypercholesterolemia-associated metabolic disorders [85].…”

“…In particular, antihyperlipidemic and antioxidant activities of this valuable fungus have been described [84], making it very attractive to combat several metabolic pathologies, such as diabetes and obesity. A recent publication investigated the transcriptome response of liver and kidney tissue from mice (C57BL/6) to a high-cholesterol diet and standardized G. lucidum extracts at the transcriptome level [85]. The extracts were isolated from fruiting bodies, which were cultivated on either a conventional substrate or substrate containing acetylsalicylic acid (ASA) as a promoter of fungal growth and secondary metabolite production.…”

Therapeutic Potential of Natural Plants Against Non-Alcoholic Fatty Liver Disease: Targeting the Interplay Between Gut Microbiota and Bile Acids

“…Furthermore, the Gl extract activated one of the major BA synthesis pathways via CYP7B1-mediated hydroxylation of cholesterol. In addition to gene modulation, the administration of Gl extracts also modulates the composition of the gut microbiota, triggering an increase in abundance of the Lactobacillaceae family and the genus Lactobacillus ( Romero-Cordoba et al., 2020 ).…”