Rottlerin suppresses lipid accumulation by inhibiting de novo lipogenesis and adipogenesis via LRP6/mTOR/SREBP1C in 3T3-L1 adipocytes

IF 3.1 3区农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Food Science and Biotechnology Pub Date : 2023-06-30 DOI:10.1007/s10068-023-01339-5

Yejin Kim, Hyun Kyung Kim, Sumin Kang, Hayoon Kim, Gwang-woong Go

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引用次数: 1

Abstract

Rottlerin is isolated from Mallotus japonicus, a plant rich in polyphenols. Rottlerin is a selective PKCδ-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 (PPARγ and C/EBPα) 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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Rottlerin通过抑制3T3-L1脂肪细胞中的LRP6/mTOR/SREBP1C的新生脂肪生成和脂肪生成来抑制脂质积累

鹿茸素是从一种富含多酚的植物Mallotus japonicus中分离出来的。Rottlerin是一种选择性pkc δ抑制剂，也被称为氧化磷酸化解偶联剂和抗肿瘤剂。然而，其抗肥胖效果尚未确定。因此，本研究在3T3-L1脂肪细胞中检测rotlerin是否通过LRP6/mTOR/SREBP1C途径抑制脂肪生成和新生脂肪生成。通过Oil Red O评估，rotlerin显著降低了脂质积累，这是支持细胞表型的证据(p < 0.001)。随后，rotlerin以剂量依赖性的方式验证了与新生脂肪形成(SREBP1C、ACC1、FAS和SCD1)和脂肪形成(PPARγ和C/EBPα)相关的关键信使RNA和蛋白质表达(p < 0.05)。进一步研究发现，rotlerin通过降低LRP6总蛋白来降低AKT/mTOR通路(p < 0.05)。总的来说，这些发现建立了rotlerin, LRP6和改变的营养传感mTOR途径之间的因果关系，其中rotlerin调节白色脂肪细胞的新生脂肪生成和脂肪生成。

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来源期刊

Food Science and Biotechnology FOOD SCIENCE & TECHNOLOGY-

CiteScore

5.40

自引率

3.40%

发文量

174

审稿时长

2.3 months

期刊介绍： The FSB journal covers food chemistry and analysis for compositional and physiological activity changes, food hygiene and toxicology, food microbiology and biotechnology, and food engineering involved in during and after food processing through physical, chemical, and biological ways. Consumer perception and sensory evaluation on processed foods are accepted only when they are relevant to the laboratory research work. As a general rule, manuscripts dealing with analysis and efficacy of extracts from natural resources prior to the processing or without any related food processing may not be considered within the scope of the journal. The FSB journal does not deal with only local interest and a lack of significant scientific merit. The main scope of our journal is seeking for human health and wellness through constructive works and new findings in food science and biotechnology field.