title: Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling.
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.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, P.O. Box 202, Volker Hall 557, 1670 University Boulevard, Birmingham, AL 35294, USA. skatiyar@uab.edu
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
authors.forename: Syed M
authors.initials: SM
authors.lastname: Meeran
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000378:metabolism / Q000528:radiation effects; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000528:radiation effects; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008820:Mice, Obese; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000528:radiation effects*; D016328:NF-kappa B / Q000378:metabolism / Q000528:radiation effects*; D009569:Nitric Oxide / Q000378:metabolism / Q000528:radiation effects; D009765:Obesity / Q000503:physiopathology*; D018384:Oxidative Stress / Q000528:radiation effects*; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione