A gold bullet to treat obesity related metabolic disorders

Abstract

Objectives: Obesity is associated with chronic low grade inflammation. Adipose resident macrophages (ATMs) in obese individuals are known to produce increased levels of proinflammatory cytokines. We have previously shown that intraperitoneal (IP) injection of 20—30 nm gold nanoparticles (AuNPs) in lean mice can induce significant fat loss along with reduced adiposetissue-derived, tumour necrosis factor (TNF) mRNA expression without a concomitant change in ATM number. This study aimed to investigate whether AuNPs also reduce fat mass and metabolic disorders in mice fed a high-fat diet (HFD). Method: Male C57BL/6 mice (6 weeks) were fed a HFD with/without daily IP injection of AuNPs (LAu 0.785 g/g/d, HAu 7.85 g/g/d) for 9 weeks. Control group was fed standard chow with vehicle injection. IP-glucose tolerance test (IP-GTT) was performed a week before the endpoint. mRNA expression of pro-inflammatory cytokines and fat metabolic markers were determined in retroperitoneal fat and liver using real-time PCR. Results: At the end point, body weight was similar between AuNP-treated and non-treated HFD-fed mice, but adiposity and liver weight were reduced by AuNP treatment. Blood glucose levels during IPGTT were significantly lower in AuNP-treated mice compared to the non-treated HFD-fed group. In addition, AuNP treatment improved plasma free fatty acid, triglyceride and cholesterol levels in HFD-fed mice. In the fat tissue, mRNA expression of pro-inflammatory markers was significantly reduced by AuNP treatment, including TNF . In the liver, AuNP treatment downregulated inflammatory markers and improved lipid metabolic markers. Interestingly, liver mRNA expression of glucose transporter-4 was upregulated by AuNP treatment. Conclusion: AuNPs treatment in HFD-fed mice prevented their development of glucose intolerance with improved fat metabolism and reduced inflammation in both the fat and liver. Our results therefore support the potential development of AuNPs as a new therapeutic strategy for obesity related metabolic disorders.