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绿茶多酚通过 erk1/2-PPARγ-脂联素通路减少高脂喂养大鼠的脂肪沉积。

Green tea polyphenols reduced fat deposits in high fat-fed rats via erk1/2-PPARγ-adiponectin pathway.

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

PLoS One. 2013;8(1):e53796. doi: 10.1371/journal.pone.0053796. Epub 2013 Jan 15.

Abstract

OBJECTIVE

Hypoadiponectinemia contributes to the development of obesity and related disorders such as diabetes, hyperlipidemia, and cardiovascular diseases. In this study we investigated the effects of green tea polyphenols (GTPs) on adiponectin levels and fat deposits in high fat (HF) fed rats, the mechanism of signaling pathway was explored as well.

METHODS AND RESULTS

Male Wistar rats were fed with high-fat diet. GTPs (0.8, 1.6, 3.2 g/L) were administered via drinking water. Serum adiponectin and insulin were measured by ELISA, mRNA levels of adiponectin and PPARγ in visceral adipose tissue (VAT) were determined by Real-time PCR, protein levels of PPARγ, phospho (p) - PPARγ, extracellular signal regulated kinase (erk) 1/2 and p-erk1/2 in VAT were determined by western blot. GTPs treatment attenuated the VAT accumulation, hypoadiponectinemia and the decreased mRNA level of adiponectin in VAT induced by HF. Decreased expression and increased phosphorylation of PPARγ (the master regulator of adiponectin), and increased activation of erk1/2 were observed in HF group, and these effects could be alleviated by GTPs treatment. To explore the underlying mechanism, VAT was cultured in DMEM with high glucose to mimic the hyperglycemia condition in vitro. Similar to the results of in vivo study, decreased adiponectin levels, decreased expression and increased phosphorylation of PPARγ, and elevated erk1/2 phosphorylation in cultured VAT were observed. These effects could be ameliorated by co-treatment with GTPs or PD98059 (a selective inhibitor of erk1/2).

CONCLUSION

GTPs reduced fat deposit, ameliorated hypoadiponectinemia in HF-fed rats, and relieved high glucose-induced adiponectin decrease in VAT in vitro. The signaling pathway analysis indicated that PPARγ regulation mediated via erk1/2 pathway was involved.

摘要

目的

低脂联素血症会导致肥胖及相关疾病的发生,如糖尿病、高血脂和心血管疾病。本研究旨在探讨绿茶多酚(GTP)对高脂饮食喂养大鼠脂联素水平和脂肪沉积的影响,并对其作用机制进行探讨。

方法和结果

雄性 Wistar 大鼠给予高脂饮食,通过饮用绿茶多酚(0.8、1.6、3.2 g/L)进行干预。采用 ELISA 法检测血清脂联素和胰岛素水平,实时 PCR 法检测内脏脂肪组织(VAT)中脂联素和过氧化物酶体增殖物激活受体γ(PPARγ)的 mRNA 水平,Western blot 法检测 VAT 中 PPARγ、磷酸化 PPARγ(p-PPARγ)、细胞外信号调节激酶(erk)1/2 和 p-erk1/2 的蛋白水平。结果表明,GTP 可减轻 HF 诱导的 VAT 堆积、脂联素血症和 VAT 中脂联素 mRNA 水平降低。HF 组 PPARγ表达降低、磷酸化增加(脂联素的主要调节因子),erk1/2 激活增加,而 GTP 可减轻这些作用。为了探讨其潜在机制,我们在体外采用高糖 DMEM 培养 VAT,结果显示,与体内研究结果相似,培养的 VAT 中脂联素水平降低、PPARγ表达和磷酸化增加、erk1/2 磷酸化增加,而 GTP 或 PD98059(erk1/2 的选择性抑制剂)共同处理可改善这些作用。

结论

GTP 可减少脂肪沉积,改善 HF 喂养大鼠的低脂联素血症,并减轻体外高糖诱导的 VAT 中脂联素减少。信号通路分析表明,erk1/2 通路介导的 PPARγ调节参与其中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d5/3546082/6a131725be7c/pone.0053796.g001.jpg

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