Obesity Increases the Risk of UV Radiation-Induced Oxidative Stress and Activation of MAPK and NF-kappaB Signaling

Free Radic Biol Med. 2007 Jan 15;42(2):299-310. doi: 10.1016/j.freeradbiomed.2006.10.049. Epub 2006 Oct 28.

Abstract

Obesity has been implicated in several diseases, including cancer; however, the relationship of obesity and susceptibility to ultraviolet (UV) radiation-caused skin diseases has not been investigated. As UV-induced oxidative stress has been implicated in several skin diseases, we assessed the role of obesity on UVB-induced oxidative stress in genetically obese Lep(ob)/Lep(ob) (leptin-deficient) mice. Here, we report that chronic exposure to UVB (120 mJ/cm(2)) resulted in greater oxidative stress in the skin of obese mice in terms of higher levels of H(2)O(2) and NO production, photo-oxidative damage of lipids and proteins, and greater depletion of antioxidant defense enzymes, like glutathione, glutathione peroxidase, and catalase. As UV-induced oxidative stress mediates activation of MAPK and NF-kappaB signaling pathways, we determined the effects of UVB on these pathways in obese mice. Exposure of obese mice to UVB resulted in phosphorylation of ERK1/2, JNK, and p38 proteins of the MAPK family. Compared to wild-type mice, the obese mice exhibited higher levels of phosphorylation of these proteins, greater activation of NF-kappaB/p65, and higher levels of circulating proinflammatory cytokines, including TNF-alpha, IL-1beta and IL-6, on UVB irradiation. Taking these results together, our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced oxidative stress and therefore may be a risk factor for skin diseases associated with UVB-induced oxidative stress.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cytokines / metabolism
  • Cytokines / radiation effects
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glutathione / metabolism
  • Glutathione / radiation effects
  • Glutathione Peroxidase / metabolism
  • Glutathione Peroxidase / radiation effects
  • Hydrogen Peroxide / metabolism
  • Hydrogen Peroxide / radiation effects
  • Immunohistochemistry
  • Lipid Peroxidation / physiology
  • Lipid Peroxidation / radiation effects
  • Mice
  • Mice, Obese
  • Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / radiation effects*
  • NF-kappa B / metabolism
  • NF-kappa B / radiation effects*
  • Nitric Oxide / metabolism
  • Nitric Oxide / radiation effects
  • Obesity / physiopathology*
  • Oxidative Stress / radiation effects*
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects*
  • Ultraviolet Rays / adverse effects*

Substances

  • Cytokines
  • NF-kappa B
  • Nitric Oxide
  • Hydrogen Peroxide
  • Glutathione Peroxidase
  • Mitogen-Activated Protein Kinases
  • Glutathione