Silicon dioxide nanoparticles inhibit the effects of cold exposure on metabolism and inflammatory responses in brown adipocytes

Abstract

Objective: Nanoparticles (NPs) in haze are potentially hazardous to health, which is more severe in the winter. Brown adipose tissue (BAT) plays important roles in obesity, insulin resistance, and diabetes. Though the toxicology of NPs has been intensively studied, few studies have been reported on the antagonistic effects between Silicon dioxide(SiO₂) NPs and cold exposure in brown adipocytes. Materials and methods: We evaluated changes by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) on metabolism genes, plasticity genes and the inflammatory responses genes in brown adipocytes in vitro. Results: The expression of adipogenic genes PRDM16, Dio2, PGC-1α and UCP1 was upregulated upon cold exposure (P < 0.05), but downregulated by SiO₂ NPs (P < 0.05). The results demonstrated that there was antagonistic effect between SiO₂ NPs and cold exposure on the plasticity genes and metabolism genes in brown adipocytes, where the main effects of SiO₂ NPs or cold exposure on the plasticity genes and metabolism genes were significant (P < 0.05). Moreover, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were upregulated by SiO₂ NPs or cold exposure (P < 0.05). The factorial analysis indicated that there was also antagonistic effect between SiO₂ NPs and cold exposure on the toxic effects in brown adipocytes, in which the main effects of cold exposure and/or SiO₂ NPs on the toxic effects were significant (P < 0.05). Conclusion: SiO₂ NPs inhibit the effect of cold exposure on metabolic genes and inflammatory responses genes in brown adipocytes.

Keywords

SiO₂ nanoparticles / cold exposure / metabolic / inflammatory response / brown adipocytes

References

[[1]] Lu S L, Feng M, Yao Z K. Physicochemical characterization and cytotoxicity of ambient coarse, fine, and ultrafine particulate matters in Shanghai atmosphere. Atmos Environ, 2011; 45(3): 736-744.

[[2]] Malfatti M A, Palko H A, Kuhn E A, et al. Determining the pharmacokinetics and long-term biodistribution of SiO₂ nanoparticles in vivo using accelerator mass spectrometry. Nano Lett, 2012; 12(11): 5532-5538.

[[3]] Li J Q, Li L, Chen H Q, et al. Application of vitamin E to antagonize SWCNTs-induced exacerbation of allergic asthma. Sci Rep, 2014; 4: 4275.

[[4]] Kang G S, Gillespie P A, Gunnison A, et al. Long-term inhalation exposure to nickel nanoparticles exacerbated atherosclerosis in a susceptible mouse model. Environ Health Perspect, 2011; 119(2): 176-181.

[[5]] Burch W M. Passage of inhaled particles into the blood circulation in humans. Circulation, 2002; 106(20): 141-141.

[[6]] Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect, 2005; 113(7): 823-839.

[[7]] Oberdorster G, Sharp Z, Atudorei V, et al. Extra pulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A, 2002; 65(20): 1531-1543.

[[8]] Simeonova P P, Erdely A. Engineered nanoparticle respiratory exposure and potential risks for cardiovascular toxicity: predictive tests and biomarkers. Inhal Toxicol, 2009; 21 Suppl 1: 68-73.

[[9]] Wen D. Nanofuel as a potential secondary energy carrier. Energy Environ Sci, 2010; 3: 591-600.

[[10]] Zou Y, Wang Y, Zhang Y, et al. Arctic sea ice, Eurasia snow, and extreme winter haze in China. Sci Adv, 2017; 3(3): e1602751.

[[11]] Dai L, Zanobetti A, Koutrakis P, et al. Associations of fine particulate matter species with mortality in the United States: a multicity time-series analysis. Environ Health Perspect, 2014; 122(8): 837-842.

[[12]] Fruijtier-Poelloth C. The toxicological mode of action and the safety of synthetic amorphous silica-a nanostructured material. Toxicology, 2012; 294(2-3): 61-79.

[[13]] Jasnic N, Djordjevic J, Djurasevic S, et al. Specific regulation of ACTH secretion under the influence of low and high ambient temperature-the role of catecholamines and vasopressin. J Thermal Biology, 2012; 37: 469-474.

[[14]] Zhang Y, Lin Y, Li X, et al. Silica dioxide nanoparticles combined with cold exposure induce stronger systemic inflammatory response. Environ Sci Pollut Res, 2017; 24(1): 291-298.

[[15]] Smorlesi A, Frontini A, Giordano A, et al. The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev, 2012; 13(Suppl 2): 83-96.

[[16]] Zhang Y, Li X, Lin Y, et al. The combined effects of silicon dioxide nanoparticles and cold air exposure on the metabolism and inflammatory responses in white adipocytes. Toxicol Res, 2017; 6(5): 705-710.

[[17]] Lin Y, Li X, Zhang L, et al. Inhaled SiO₂ nanoparticles blunt cold exposure induced WAT browning and metabolism activation in white and brown adipose tissue. Toxicol Res, 2016; 5(4): 1106-1114.

[[18]] Ricquier D. Respiration uncoupling and metabolism in the control of energy expenditure. Proc Nutr Soc, 2005; 64(1): 47-52.

[[19]] Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev, 2004; 84(1): 277-359.

[[20]] Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab, 2007; 6(1): 38-54.

[[21]] Seale P, Bjork B, Yang W, et al. PRDM16 controls a brown fat/ skeletal muscle switch. Nature, 2008; 454(7207): 961-967.

[[22]] Puigserver P, Wu Z, Park C W, et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998; 92(6): 829-839.

[[23]] Wu Z, Boss O. Targeting PGC-1 alpha to control energy homeostasis. Expert Opin Ther Targets, 2007; 11(10): 1329-1338.

[[24]] Obregon M J. Thyroid hormone and adipocyte differentiation. Thyroid, 2008; 18(2): 185-195.

[[25]] Bianco A C, Kim B W. Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest, 2006; 116(10): 2571-2579.

[[26]] Xu H, Barnes G T, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest, 2003; 112(12): 1821-1830.

[[27]] Lumeng C N, DelProposto J B, Westcott D J, et al. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes, 2008; 57(12): 3239-3246.

[[28]] Olefsky J M, Glass C K. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol, 2010; 72: 219-246.

[[29]] Xu H, Sethi J K, Hotamisligil G S. Transmembrane tumor necrosis factor TNF-alpha inhibits adipocyte differentiation by selectively activating TNF receptor 1. J Biol Chem, 1999; 274(37): 26287-26295.

[[30]] Galic S, Oakhill J S, Steinberg G R. Adipose tissue as an endocrine organ. Mol Cell Endocrinol, 2010; 316(2): 129-139.

[[31]] Ye L, Wu J, Cohen P, et al. Fat cells directly sense temperature to activate thermogenesis. Proc Natl Acad Sci U S A, 2013; 110(30): 12480-12485.

[[32]] Enerback S. Human brown adipose tissue. Cell Metab, 2010; 11(4): 248-252.

[[33]] Nedergaard J, Cannon B. The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab, 2010; 11(4): 268-272.

[[34]] Bourdon J A, Halappanavar S, Saber A T, et al. Hepatic and pulmonary toxicogenomic profiles in mice intratracheally instilled with carbon black nanoparticles reveal pulmonary inflammation, acute phase response, and alterations in lipid homeostasis. Toxicol Sci, 2012; 127(2): 474-484.

[[35]] Li M, Li Q, Yang G, et al. Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism. J Allergy Clin Immunol, 2011; 128(3): 626-634.

[[36]] Crosswhite P, Sun Z J. Ribonucleic acid interference knockdown of interleukin 6 attenuates cold-induced hypertension. Hypertension, 2010; 55(6): 1484-1491.

[[37]] Friedman J M. Leptin at 14 y of age: an ongoing story. Am J Clin Nutr, 2009; 89(3): 973S-979S.

[[38]] Rosen E D, Spiegelman B M. Adipocytes as regulators of energy balance and glucose homeostasis. Nature, 2006; 444(7121): 847-853.

[[39]] Coppack S W. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc, 2001; 60(3): 349-356.

[[40]] Hardardottir I, Gruenfeld C, Feingold K R. Effects of endotoxin and cytokines on lipid metabolism. Curr Opin Lipidol, 1994; 5(3): 207-215.

[[41]] Granneman J G, Burnazi M, Zhu Z, et al. White adipose tissue contributes to UCP1-independent thermogenesis. Am J Physiol Endocrinol Metab, 2003; 285(6): E1230-E1236.