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Hypolipidemic Activity of Quercus acutissima Fruit Ethanol Extract is Mediated by Inhibition of Acetylation

Journal of Medicinal Food 2017년 20권 6호 p.542 ~ 549
황진택, 최호경, 김성희, 정상원, 허행전, 박재호, 정민유,
소속 상세정보
황진택 ( Hwang Jin-Taek ) - Korea Food Research Institute
최호경 ( Choi Hyo-Kyoung ) - Korea Food Research Institute
김성희 ( Kim Sung-Hee ) - Korea Food Research Institute
정상원 ( Chung Sang-Won ) - Korea Food Research Institute
허행전 ( Hur Haeng-Jeon ) - Korea Food Research Institute
박재호 ( Park Jae-Ho ) - Korea Food Research Institute
정민유 ( Chung Min-Yu ) - Korea Food Research Institute

Abstract


The acetylation of histone and nonhistone proteins is associated with adipogenesis. The objective of the present study was to investigate whether an ethanol extract of Quercus acutissima fruit (QF) exhibits antiobesity effects through inhibition of acetylation in 3T3-L1 preadipocytes and high fat diet (HFD)-fed obese mice. We observed that QF acts as a histone acetyltransferase (HAT) inhibitor and that QF (400?μg/mL) markedly inhibits the activity of p300 and CREB-binding protein. QF (200?μg/mL) significantly attenuated lipid accumulation without apparent toxicity, which is likely attributable to a decrease in the expressions of lipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor gamma, sterol regulatory element-binding protein 1, and CCAAT-enhancer-binding proteins alpha that were otherwise increased by MDI (a hormonal cocktail containing methyl isobutylmethylxanthine, dexamethasone, and insulin). MDI increased the acetylation of total lysine residues in whole 3T3-L1 cell lysate, an effect that was reversed by QF treatment (200?μg/mL). To further confirm the antiobesity activity of QF, mice were fed with HFD supplemented with QF at 50 and 200?mg/kg body weight. Mice fed with HFD exhibited increased masses of body, liver, and retroperitoneal fat, an effect that was suppressed in the presence of QF supplementation. QF-mediated decreases in body weight were attributable to a decrease in the average size of lipid droplets, as well as lipid accumulation in retroperitoneal fat and the liver, respectively. QF-mediated reductions in the size of the lipid droplets in the retroperitoneal fat tissue were likely associated with decreased expression of DGAT2. Taken together, our observations suggest that QF acts as an HAT inhibitor and attenuates adipogenesis in 3T3-L1 preadipocytes, resulting in the mitigation of HFD-induced obesity.

키워드

histone acetyltransferase; p300; Quercus acutissima fruit; retroperitoneal fat; DGAT2

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