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牛叠肚通过Akt调节脂肪生成并抑制大鼠高脂饮食诱导的肥胖。

Rubus crataegifolius Bunge regulates adipogenesis through Akt and inhibits high-fat diet-induced obesity in rats.

作者信息

Jung Min-Sup, Lee Soo-Jung, Song Yuno, Jang Sun-Hee, Min Wongi, Won Chung-Kil, Kim Hong-Duck, Kim Tae Hoon, Cho Jae-Hyeon

机构信息

Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701 Korea.

Department of Foods and Nutrition, Gyeongsang National University, Jinju, 660-701 Korea.

出版信息

Nutr Metab (Lond). 2016 Apr 27;13:29. doi: 10.1186/s12986-016-0091-0. eCollection 2016.

Abstract

BACKGROUND

Obesity is one of the greatest public health problems and major risk factors for serious metabolic diseases and significantly increases the risk of premature death. The aim of this study was to determine the inhibitory effects of Rubus crataegifolius Bunge (RCB) on adipocyte differentiation in 3 T3-L1 cells and its anti-obesity properties in high fat diet (HFD)-induced obese rats.

METHODS

3 T3-L1 adipocytes and HFD-induced obese rats were treated with RCB, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments.

RESULTS

RCB treatment significantly inhibited adipocyte differentiation by suppressing the expression of C/EBPβ, C/EBPα, and PPARγ in the 3 T3-L1 adipocytes. Subsequently, the expression of the PPARγ target genes aP2 and fatty acid synthase (FAS) decreased following RCB treatment during adipocyte differentiation. In uncovering the specific mechanism that mediates the effects of RCB, we demonstrated that the insulin-stimulated phosphorylation of Akt strongly decreased and that its downstream substrate phospho-GSK3β was downregulated following RCB treatment in the 3 T3-L1 adipocytes. Moreover, LY294002, an inhibitor of Akt phosphorylation, exerted stronger inhibitory effects on RCB-mediated suppression of adipocyte differentiation, leading to the inhibition of adipocyte differentiation through the downregulation of Akt signaling. An HFD-induced obesity rat model was used to determine the inhibitory effects of RCB on obesity. Body weight gain and fat accumulation in adipose tissue were significantly reduced by the supplementation of RCB. Moreover, RCB treatment caused a significant decrease in adipocyte size, associated with a decrease in epididymal fat weight. The serum total cholesterol (TC) and triglyceride (TG) levels decreased in response to RCB treatment, whereas HDL cholesterol (HDL-C) increased, indicating that RCB attenuated lipid accumulation in adipose tissue in HFD-induced obese rats.

CONCLUSION

Our results demonstrate an inhibitory effect of RCB on adipogenesis through the reduction of the adipogenic factors PPARγ, C/EBPα, and phospho-Akt. RCB had a potent anti-obesity effect, reducing body weight gain in HFD-induced obese rats.

摘要

背景

肥胖是最严重的公共卫生问题之一,也是严重代谢性疾病的主要危险因素,显著增加过早死亡风险。本研究旨在确定山楂叶悬钩子(RCB)对3T3-L1细胞脂肪细胞分化的抑制作用及其对高脂饮食(HFD)诱导的肥胖大鼠的抗肥胖特性。

方法

用RCB处理3T3-L1脂肪细胞和HFD诱导的肥胖大鼠,并通过RT-PCR和蛋白质印迹实验分析其对基因表达的影响。

结果

RCB处理通过抑制3T3-L1脂肪细胞中C/EBPβ、C/EBPα和PPARγ的表达,显著抑制脂肪细胞分化。随后,在脂肪细胞分化过程中,RCB处理后PPARγ靶基因aP2和脂肪酸合酶(FAS)的表达降低。在揭示介导RCB作用的具体机制时,我们证明在3T3-L1脂肪细胞中,RCB处理后胰岛素刺激的Akt磷酸化显著降低,其下游底物磷酸化GSK3β下调。此外,Akt磷酸化抑制剂LY294002对RCB介导的脂肪细胞分化抑制作用更强,通过下调Akt信号通路导致脂肪细胞分化受到抑制。使用HFD诱导的肥胖大鼠模型来确定RCB对肥胖的抑制作用。补充RCB可显著减少体重增加和脂肪组织中的脂肪堆积。此外,RCB处理导致脂肪细胞大小显著减小,附睾脂肪重量降低。RCB处理后血清总胆固醇(TC)和甘油三酯(TG)水平降低,而高密度脂蛋白胆固醇(HDL-C)升高,表明RCB减轻了HFD诱导的肥胖大鼠脂肪组织中的脂质堆积。

结论

我们的结果表明,RCB通过减少成脂因子PPARγ、C/EBPα和磷酸化Akt对脂肪生成具有抑制作用。RCB具有强大的抗肥胖作用,可减少HFD诱导的肥胖大鼠的体重增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/382e/4847245/60a34902d5b4/12986_2016_91_Fig1_HTML.jpg

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