8-Oxo-2'-deoxyguanosine ameliorates features of metabolic syndrome in obese mice

Biochem Biophys Res Commun. 2014 Jan 10;443(2):610-6. doi: 10.1016/j.bbrc.2013.12.018. Epub 2013 Dec 11.

Abstract

Metabolic syndrome describes a group of clinical features that together increase the incidence of coronary artery disease, stroke and type 2 diabetes. Insulin resistance is a major risk factor for developing metabolic syndrome. A chronic state of inflammation accompanies the accumulation of surplus lipids in adipose and liver tissue, frequently involved in insulin resistance. 8-Oxo-2'-deoxyguanosine (8-Oxo-dG) is a potent anti-inflammatory agent that inactivates both Rac1 and Rac2 which are critical to initiating the inflammatory responses in various cell types, including macrophages. In this study, we explored whether 8-Oxo-dG suppressed a series of systemic inflammatory cascades, resulting in the amelioration of typical features of metabolic syndrome in obese mice. The results demonstrate that 8-Oxo-dG effectively improved hyperglycemia, dyslipidemia and fatty liver changes in obese mice. The level of biochemical markers indicative of systemic inflammation were reduced in 8-Oxo-dG treated mice, whereas serum levels of adiponectin, a crucial factor associated with improved metabolic syndrome, were enhanced. Our results demonstrate that 8-Oxo-dG effectively disrupts the pathogenesis of insulin resistance and obesity-associated metabolic syndrome.

Keywords: 8-Oxo-deoxyguanosine; Inflammation; Insulin resistance; Metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Cytokines / immunology*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / therapeutic use
  • Male
  • Metabolic Syndrome / immunology*
  • Metabolic Syndrome / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / immunology*
  • Obesity / prevention & control*
  • Treatment Outcome

Substances

  • Cytokines
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine