Objective To explore the possible key role of Plin1 gene in the action of quercetin on lipid metabolism and AMPK/SREBP1 pathway related mRNA and protein expressions in MAFLD mice. Methods Twenty-four 4 w-old male C57BL/6J mice were divided into three groups: control group (C), MAFLD model group (M), and 400 mg/(kg·bw·d )quercetin treatment group (400Q). Twenty-four C57BL/6J male Plin1 knockout mice were divided into three groups: knockout control group (KO-C), knockout model group (KO-M), and 400 mg/(kg·bw·d) quercetin knockout model group (KO-400Q), with 8 mice in each group. Group C and KO-C were fed a normal diet, and the other four groups were fed a 60% high-fat diet. The 400Q and KO-400Q groups were given 40 mg/ml quercetin solution by gavage, and the other four groups were given normal saline by gavage. The volume of quercetin solution was calculated as 10 μl/g according to the body weight of the mice. The mice were sacrificed after feeding for 12 weeks. The body weight and liver weight were recorded. The levels of TC, TG, ALT and AST in serum and liver were detected. Liver lipid droplets were checked after oil red Ο staining. The protein and mRNA expression levels of PLIN1, AMPK, SREBP1, FASN, SCD1 and ACC1 in the liver were measured. Results Compared with the group M, the body weight, serum and liver TC, TG, ALT, AST and lipid droplets in the liver were decreased, and the expressions of Plin1 mRNA and protein were increased after quercetin intervention (P<0.05). After Plin1 gene knockout, serum and liver TC, TG, ALT, AST levels were increased (P<0.05). The AMPK mRNA expression was increased and the mRNA expression of SREBP1 and its downstream lipid synthesis genes decreased in the 400Q and KO-C groups (P<0.05). The serum and liver TC, TG, ALT and AST levels, liver weight and index of the KO-400Q group were increased. The liver lipid droplets were increased, while the expression of AMPK mRNA was decreased, and the mRNA expression of SREBP1 and its downstream lipid synthesis genes were increased (P<0.05). Conclusion Quercetin treatment improves liver lipid accumulation in MAFLD mice. Knockout of Plin1 abolished the protective effect of quercetin. Quercetin exerts its protective effects possibly by regulating Plin1 gene expression and affecting AMPK/SREBP1 pathway related mRNA and protein expression in MAFLD mice.
Key words
quercetin /
metabolic associated fatty liver disease /
Plin1 gene knockout /
mice
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