Effects of Long-Term High-Ergosterol Intake on the Cholesterol and Vitamin D Biosynthetic Pathways of Rats Fed a High-Fat and High-Sucrose Diet

Abstract

Dyslipidemia is a lifestyle-related (physical inactivity or obesity) disease; therefore, dietary foods that can easily be consumed in daily life is important to prevent dyslipidemia. Ergosterol, a precursor of vitamin D₂, is a fungal sterol present in the membranes of edible mushrooms and other fungi. Ergosterol is converted to brassicasterol by 7-dehydrocholesterol reductase (DHCR7), a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D₃) into cholesterol. Previously, we reported that ergosterol increases 7-dehydrocholesterol, decreases cholesterol levels by competitive effect of DHCR7, and reduces DHCR7 mRNA and protein levels in human HepG2 hepatoma cells. Here, we investigated the effects of long-term high ergosterol intake on the cholesterol, vitamin D₂, and D₃ biosynthetic pathways of rats fed a high-fat and high-sucrose (HFHS) diet using GC–MS and LC with tandem mass spectrometry. In HFHS rats, oral ergosterol administration for 14 weeks significantly decreased plasma low-density lipoprotein cholesterol, total bile acid, and cholesterol precursor (squalene and desmosterol) levels and increased 7-dehydrocholesterol levels compared to HFHS rats without ergosterol. Ergosterol, brassicasterol, and vitamin D₂ were detected, cholesterol levels were slightly decreased, and levels of vitamin D₃ and its metabolites were slightly increased in rats fed HFHS with ergosterol. These results showed that ergosterol increased vitamin D₂ levels, inhibited the cholesterol biosynthetic pathway, and possibly promoted vitamin D₃ biosynthesis in vivo. Therefore, daily ergosterol intake may aid in the prevention of dyslipidemia.