TREATING OBESITY RELATED METABOLIC DISORDERS USING GOLD NANOPARTICLES — The Association Specialists
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TREATING OBESITY RELATED METABOLIC DISORDERS USING GOLD NANOPARTICLES (401)

Jane Phui Mun Ng 1 , Stella M Valenzuela 1 2 , Hui Chen 1 2 , Michael Cortie 3 , Andrew M McDonagh 4 , Bruce K Milthorpe 2
  1. School of Medical and Molecular Sciences, University of Technology Sydney, Sydney, NSW, Australia
  2. Centre of Health Technologies, University of Technology Sydney, Sydney, NSW, Australia
  3. Institiute for Nanoscale Technology, University of Technology Sydney, Sydney, NSW, Australia
  4. School of Chemistry and Forensic Science, University of Technology Sydney, Sydney, NSW, Australia

Objectives: We have previously shown that 20-30nm gold nanoparticles (AuNPs) can induce significant fat loss and inhibit inflammatory cytokine production in fat tissue, following intraperitoneal injection in mice. Our current work aims to determine the mechanism of this action using in vitro cell models in order to study the direct action of AuNPs on adipocytes and macrophages.

Methods: Murine RAW264.7 macrophages and 3T3-L1 mature adipocytes were treated with AuNPs (31.5, 3.15 & 0.315 µg/mL) for 1h, 24h and 72h. Gene and protein expression of a number of inflammatory cytokines and lipid metabolic markers were determined using real-time PCR and western blotting, respectively from each cell line. Cellular oxidative stress was studied using H2DCF-DA (dihydrodichlorofluorescein diacetate) measuring reactive oxygen species (ROS) levels. Free fatty acids (FFA) and triglycerides were measured in the adipocytes and culture supernatant.

Result: AuNPs demonstrated no cytotoxic effects on either cell lines. AuNPs did not significantly alter the inflammatory cytokine expression (TNFα, IL-1β and IL-6) in RAW264.7, nor were any changes noted in the protein expression of IKK α/β for the activation of NFkB pathway. However, exposure of RAW264.7 to AuNPs resulted in decreased levels of ROS. Interestingly, AuNPs down-regulated mRNA expression of the adipocyte differentiation marker, peroxisome proliferator-activated receptor gamma (PPARg), and the fatty acid metabolic markers, carnitine palmitoyltransferase-1 (CPT-1) and adipose triglyceride lipase (ATGL). Intracellular FFA and triglyceride levels were also found to be significantly increased following AuNP treatment for 1h and 24h.

Conclusion: The in vivo down-regulation of pro-inflammatory cytokine expression seen in our earlier studies may be attributed to the presence of FFAs, warranting further investigation. The antioxidant effect of AuNPs on macrophages and their regulation of adipocyte metabolic markers preventing lipolysis and FFA oxidation, further supports their versatility as a treatment strategy for obesity related metabolic disorders.