KMID : 1007520230320101445
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Food Science and Biotechnology 2023 Volume.32 No. 10 p.1445 ~ p.1452
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Rottlerin suppresses lipid accumulation by inhibiting de novo lipogenesis and adipogenesis via LRP6/mTOR/SREBP1C in 3T3-L1 adipocytes
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Kim Ye-Jin
Kim Hyun-Kyung Kang Su-Min Kim Ha-Yoon Go Gwang-Woong
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Abstract
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Rottlerin is isolated from Mallotus japonicus, a plant rich in polyphenols. Rottlerin is a selective PKC¥ä-inhibitor and is also known as an uncoupler of oxidative phosphorylation and anti-neoplastic agent. However, its anti-obesity effect is yet to be established. Therefore, this study tested whether rottlerin inhibits adipogenesis and de novo lipogenesis via the LRP6/mTOR/SREBP1C pathway in 3T3-L1 adipocytes. Rottlerin dramatically decreased lipid accumulation assessed by Oil Red O as evidence to support the cellular phenotype (p?0.001). Pivotal messenger RNA and protein expressions associated with de novo lipogenesis (SREBP1C, ACC1, FAS, and SCD1) and adipogenesis (PPAR¥ã and C/EBP¥á) were subsequentially verified by rottlerin in a dose-dependent manner (p?0.05). Further investigation revealed that rottlerin reduced the AKT/mTOR pathway via diminished total protein of LRP6 (p?0.05). Collectively, these findings establish a causal link between rottlerin, LRP6, and the altered nutrient-sensing mTOR pathway, in which rottlerin regulates de novo lipogenesis and adipogenesis in white adipocytes.
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KEYWORD
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Rottlerin, Adipogenesis, De novo lipogenesis, 3T3-L1 adipocytes, The nutrient-sensing mTOR pathway
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