Nanoformulated copper/zinc superoxide dismutase reduces adipose inflammation in obesity

Obesity (Silver Spring). 2016 Jan;24(1):148-56. doi: 10.1002/oby.21348. Epub 2015 Nov 27.

Abstract

Objective: An intimate association exists between oxidative stress and inflammation. Because adipose tissue (AT) inflammation is intricately linked to metabolic disorders, it was hypothesized that reducing oxidative stress would be effective in ameliorating AT inflammation in obesity.

Methods: Wild-type mice were fed a high-fat diet (HF) for 8 weeks followed by a 2-week treatment with nanoformulated copper/zinc superoxide dismutase (NanoSOD). The mice were divided into: 1) chow diet, 2) HF, and 3) HF + NanoSOD.

Results: The HF + NanoSOD-treated mice showed a significant decrease in plasma and liver triglycerides when compared with HF-fed mice. Interestingly, NanoSOD reduced the expression of macrophage and inflammatory markers in visceral AT (VAT) and stromal cells derived from VAT. Moreover, the activation of proinflammatory signaling pathways, in particular, the extracellular signal-regulated kinases, was blunted in VAT on NanoSOD treatment. However, markers of oxidative stress were not altered significantly in the HF + NanoSOD group in the experimental conditions. Pretreatment of either macrophages or adipocytes significantly reduced the inflammatory response invoked in an in vitro coculture system, further supporting the role of NanoSOD in inhibiting obesity-linked inflammation.

Conclusions: This data suggest that NanoSOD is effective not only in reducing AT macrophage accumulation and AT inflammation but also in promoting triglyceride metabolism in obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Adiposity / drug effects
  • Animals
  • Diet, High-Fat
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Lipid Metabolism / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage
  • Obesity / complications
  • Obesity / metabolism
  • Obesity / pathology*
  • Superoxide Dismutase / administration & dosage
  • Superoxide Dismutase / pharmacology*
  • Triglycerides / blood

Substances

  • Triglycerides
  • Superoxide Dismutase
  • Extracellular Signal-Regulated MAP Kinases