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金纳米颗粒改善高脂肪饮食喂养的小鼠的代谢特征。

Gold nanoparticles improve metabolic profile of mice fed a high-fat diet.

机构信息

Molecular Biosciences Team, School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.

Centre for Health Technology, University of Technology Sydney, Sydney, NSW, 2007, Australia.

出版信息

J Nanobiotechnology. 2018 Feb 6;16(1):11. doi: 10.1186/s12951-018-0338-1.

Abstract

BACKGROUND

Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The anti-inflammatory property of gold compounds has been used in treating rheumatoid arthritis in the clinic. Previously we found that pure gold nanoparticles (AuNPs, 21 nm) also possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. However, whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The study employed C57BL/6 mice fed a pellet high fat diet (HFD, 43% as fat) that were treated daily with AuNPs [low (HFD-LAu) or high (HFD-HAu) dose] via intraperitoneal injection for 9 weeks. In the in vitro study, RAW264.7 macrophages and 3T3-L1 adipocytes were cultured with low and high concentrations of AuNPs alone or together.

RESULTS

The HFD-fed mice showed a significant increase in fat mass, glucose intolerance, dyslipidemia, and liver steatosis. The HFD-LAu group showed an 8% reduction in body weight, ameliorated hyperlipidemia, and normal glucose tolerance; while the HFD-HAu group had a 5% reduction in body weight with significant improvement in their glucose intolerance and hyperlipidemia. The underlying mechanism may be attributed to a reduction in adipose and hepatic local proinflammatory cytokine production, e.g. TNFα. In vitro studies of co-cultured murine RAW264.7 macrophage and 3T3-L1 adipocytes supported this proposed mechanism.

CONCLUSION

AuNPs demonstrate a promising profile for potential management of obesity related glucose and lipid disorders and are useful as a research tool for the study of biological mechanisms.

摘要

背景

肥胖是多种代谢紊乱的高危因素,这是由于能量、葡萄糖和脂质的过度摄入,而这些通常来自于西方饮食。低度炎症在代谢紊乱的进展中起着关键作用。金化合物的抗炎特性已在临床上用于治疗类风湿性关节炎。先前我们发现,通过下调肿瘤坏死因子 (TNF)α,腹腔内注射 21nm 纯金纳米粒子 (AuNPs) 也对腹腔注射后的腹膜后脂肪组织具有抗炎作用。然而,这种作用是否能改变肥胖者发生代谢紊乱的风险尚未得到很好的研究。该研究采用 C57BL/6 小鼠,给予高脂饮食(HFD,脂肪含量 43%),并通过腹腔内注射每日给予低剂量(HFD-LAu)或高剂量(HFD-HAu)的 AuNPs,共 9 周。在体外研究中,RAW264.7 巨噬细胞和 3T3-L1 脂肪细胞分别用低浓度和高浓度的 AuNPs 单独或联合培养。

结果

HFD 喂养的小鼠体脂增加,葡萄糖耐量受损,血脂异常和肝脂肪变性。HFD-LAu 组体重减轻 8%,改善了高脂血症和正常葡萄糖耐量;而 HFD-HAu 组体重减轻 5%,葡萄糖耐量和高脂血症明显改善。其潜在机制可能是由于脂肪和肝脏局部促炎细胞因子的产生减少,例如 TNFα。共培养的鼠 RAW264.7 巨噬细胞和 3T3-L1 脂肪细胞的体外研究支持了这一提出的机制。

结论

AuNPs 为肥胖相关的葡萄糖和脂质代谢紊乱的管理提供了有希望的前景,并且可用作研究生物机制的研究工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ae9/5800098/719ad980c410/12951_2018_338_Fig1_HTML.jpg

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