Gold nanoparticles as cell regulators: beneficial effects of gold nanoparticles on the metabolic profile of mice with pre-existing obesity

Abstract

Background: We have previously shown that intraperitoneal injection of gold nanoparticles (AuNPs, 20-30 nm) into mice, decreases high-fat diet (HFD) induced weight gain and glucose intolerance, via suppression of inflammatory responses in both fat and liver tissues. This study investigates whether AuNPs provide similar benefit to mice with pre-existing obesity. Male C57BL/6 mice were fed a HFD for 15 weeks. AuNPs (OB-EAu 0.0785 μg/g/day, OB-LAu 0.785 μg/g/day, OB-HAu7.85 μg/g/day, ip) were administered to subgroups of HFD-fed mice over the last 5 weeks. Control group was fed standard chow and administered vehicle injection.

Results: Only the OB-LAu group demonstrated significant weight loss (12%), while all AuNP treated groups showed improved glycaemic control and reduced blood lipid levels. In the fat tissue, mRNA expression of pro-inflammatory markers were unchanged following AuNP treatment, while glucose and lipid metabolic markers were improved in OB-LAu and OB-HAu mice. In the liver, AuNP treatment downregulated inflammatory markers and improved lipid metabolic markers, with marked effects in OB-EAu and OB-LAu groups.

Conclusions: AuNP treatment can improve glucose and fat metabolism in mice with long-term obesity, however weight loss was only observed in a single specific dose regime. AuNP therapy is a promising new technology for managing metabolic disorders in the obese.

Keywords: Gold nanoparticles; Inflammation; Liver; Metabolism; Obesity.

Fig. 1

Effect of HFD and AuNP treatment on pro-inflammatory markers in abdominal fat and liver. mRNA expression of F4/80 (a, d), TNFα (b, e), and TLR-4 (c, f) in Chow, OB, OB-EAu, OB-LAu and OB-HAu mice at 15 weeks. Results are expressed as mean ± S.E.M. Data were analyzed by one-way ANOVA followed by post hoc Bonferroni test; *P < 0.05, **P < 0.01 vs Chow; ^†P < 0.05, ^††P < 0.01 vs OB. Data analyzed with conditional student t test followed by Welch correction, τ P < 0.05 vs Chow; n = 5–8

Fig. 2

Effect of HFD and AuNP treatment on lipid and glucose metabolic markers in the fat. mRNA expression of FOX-O1 (a), GLUT-4 (b), adiponectin (c), PPARγ (d), SREBP-1c (e), FASN (f), ATGL (g), and CPT-1α (h) in Chow, OB, OB-EAu, OB-LAu and OB-HAu mice. Results are expressed as mean ± S.E.M. Data were analysed by one-way ANOVA followed by post hoc Bonferroni test. *P < 0.05, **P < 0.01 vs Chow; ^†P < 0.05, ^††P < 0.01 vs OB; Data analysed with conditional student t test followed by Welch correction, τ P < 0.05 vs Chow; n = 6–8

Fig. 3

Effect of HFD and AuNP treatment on lipid and glucose metabolic markers in the liver. mRNA expression of FOX-O1 (a), PERCK (b), GLUT-4 (c), PPARγ (d), SREBP-1c (e), FASN (f), ATGL (g), and CPT-1α (h) in Chow, OB, OB-EAu, OB-LAu and OB-HAu mice. Results are expressed as mean ± S.E.M. Data were analysed by one-way ANOVA followed by post hoc Bonferroni test. *P < 0.05, **P < 0.01 vs Chow; ^†P < 0.05, P < 0.01 vs OB; n = 5–8