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

Br J Nutr. 2023 Sep 13:1-27. doi: 10.1017/S0007114523001344. Online ahead of print.ABSTRACTSterol 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.PMID:37699661 | DOI:10.1017/S0007114523001344
Source: The British Journal of Nutrition - Category: Nutrition Authors: Source Type: research