Dietary Ganoderma lucidum Modulates Liver and Adipose Tissue Responses in Western Diet-Fed C57BL/6J Mice

Sustained consumption of Western-style diets (WDs), rich in fat and cholesterol, challenges metabolic homeostasis and results in organ-specific alterations, notably hepatic lipid accumulation and adipose tissue dysfunction. Medicinal mushrooms such as Ganoderma lucidum have gained attention for their biological activities; however, the extent to which nutritionally realistic dietary intake of G. lucidum modulates tissue-specific metabolic adaptation under obesogenic conditions remains poorly defined. This exploratory study aimed to evaluate how dietary supplementation with a Ganoderma lucidum extract (GLE) modulates metabolic and organ-specific responses in a WD-fed preclinical mouse model. Forty-seven male C57BL/6J mice were assigned to five groups receiving a control diet (CTR), a cholesterol-enriched WD, or the WD supplemented with increasing concentrations of GLE (0.7%, 1.4%, or 2.8%). Over thirteen weeks, body mass and food and water intake were monitored weekly. Afterwards, mice were euthanized, and tissue and blood samples were collected for further analysis. Fasting glucose was lower in WD+2.8% GLE than in CTR, although no GLE-supplemented group differed significantly from WD and glucose tolerance was unchanged. All GLE-supplemented groups had a lower hepatic genetic damage index than WD. WD+1.4% GLE showed a higher frequency of localized periportal hepatic vacuolar changes than WD, whereas WD+2.8% GLE had lower relative liver weight. GLE supplementation was also associated with depot-specific variation in the occurrence of multilocular adipocytes with a beige-like appearance, without significant changes in final body mass or adiposity. In this preclinical model, subchronic dietary GLE was associated with selected tissue-specific differences, most consistently lower hepatic DNA damage and depot-specific variation in multilocular adipocyte morphology, without consistent systemic metabolic improvements.