Abstract

BackgroundObesity 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.ResultsThe 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.ConclusionAuNPs 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.

Highlights

  • Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet

  • The two groups of mice treated with AuNPs consumed more energy than the Chow-C and highfat diet (HFD)-C groups (P < 0.05, Table 1)

  • The body weights of the HFD-LAu and HFD-HAu groups were 8 and 5% smaller than the HFD-C mice, respectively (P < 0.05)

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Summary

Introduction

Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. We found that pure gold nanoparticles (AuNPs, 21 nm) possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. Whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The current global surge in obesity has seen a staggering 800% increase in demand for weight-loss surgical procedures over the last decade, as a means of controlling these metabolic disorders [1] This increase is driven by the disappointingly low success rate of weight-loss medications and interventions, as well as the difficulties faced by individuals trying to maintain ideal. The function and toxicity of AuNPs differ subtantially depending on the size and shape with AuNPs larger than 15 nm comparatively nontoxic [5]

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