Luteolin, a naturally derived flavonoid, exerts beneficial effects such as antitumor, antioxidant, and anti-inflammatory effects. However, the molecular mechanism underlying the effect of luteolin in hypercholesterolemia remains unclear. In this study, we demonstrated that luteolin upregulated the expression of liver X receptor (LXR) α, ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B member 1 (SRB1), which play a major role in cholesterol efflux, in HepG2 hepatocytes. Luteolin-stimulated expression of ABCG1 and SRB1 was reversed by inhibitory compound of LXRα. Luteolin administration also upregulated the expression of ABCG1, and SRB1 as well as cholesterol 7 α-hydroxylase (Cyp7α1) in the liver of diet-induced obese mice. Luteolin decreased the level of blood cholesterol and non-high-density lipoprotein cholesterol in obese mice. In addition, luteolin ameliorated glucose intolerance and reduced expression of gluconeogenesis-associated enzymes in an LXRα-dependent manner. PRACTICAL APPLICATIONS: Luteolin is known to possess various pharmacological activities. This research revealed that luteolin ameliorates hypercholesterolemia and glucose intolerance in diet-induced obesity. The results indicate that the potential properties of luteolin in cholesterol metabolism could be explained, at least in part, as being due to upregulated expression of ABCG1, and SRB1 through activation of liver X receptor, LXRα signaling pathway in HepG2 cells.
Keywords: LXRα; cholesterol metabolism; diet-induced obesity; gluconeogenesis; luteolin.
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