Dietary palm oil enhances SREBP2-mediated cholesterol biosynthesis through inducing endoplasmic reticulum stress in muscle of large yellow croaker ( Larimichthys crocea)

Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control Cholesterol homeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterization of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and 7-dehydrocholesterol reductase (DHCR7) which were rate-limiting Enzymes of Cholesterol biosynthesis. Moreover, dietary palm oil (PO) in vivo or palmitic acid (PA) treatment in vitro elevated Cholesterol content through triggering SREBP2-mediated Cholesterol biosynthesis in large yellow croaker. Furthermore, our results also found that PA-induced activation of SREBP2 was dependent on the stimulating of endoplasmic reticulum stress (ERS) in croaker myocytes and inhibition of ERS by 4-Phenylbutyric acid alleviated PA-induced SREBP2 activation and Cholesterol biosynthesis. In summary, our findings reveal a novel insight for understanding the role of SREBP2 in regulation of Cholesterol metabolism in fish and may deepen the link between dietary fatty acid and Cholesterol biosynthesis.