Nrf2 activation by hydroxytyrosol and dimethyl fumarate ameliorates skin tissue repair in high-fat diet-fed mice by promoting M2 macrophage polarization and normalizing inflammatory response and oxidative damage.
Regina Viana de Carvalho FariaMatheus Silva DuarteJeane de Souza NogueiraBianca Martins GregórioBruna Romana-SouzaPublished in: Journal of biochemical and molecular toxicology (2024)
Hydroxytyrosol (HT) or dimethyl fumarate (DMF), activators of nuclear factor erythroid 2-related factor 2 (Nrf2), may reduce obesity in high-fat diet (HFD)-fed animals; nevertheless, the role of these activators on skin tissue repair of HFD-fed animals was not reported. This study investigated whether HT or DMF could improve skin wound healing of HFD-fed obese animals. Mice were fed with an HFD, treated with HT or DMF, and full-thickness skin wounds were created. Macrophages isolated from control and obese animals were treated in vitro with HT. DMF, but not HT, reduced the body weight of HFD-fed mice. Collagen deposition and wound closure were improved by HT or DMF in HFD-fed animals. HT or DMF increased anti-inflammatory macrophage phenotype and protein Nrf2 levels in wounds of HFD-fed mice. Lipid peroxidation and protein tumor necrosis factor-α levels were reduced by HT or DMF in wounds of HFD-fed animals. In in vitro, HT stimulated Nrf2 activation in mouse macrophages isolated from obese animals. In conclusion, HT or DMF improves skin wound healing of HFD-fed mice by reducing oxidative damage and inflammatory response. HT or DMF may be used as a therapeutic strategy to improve the skin healing process in individuals with obesity.
Keyphrases
- high fat diet
- wound healing
- insulin resistance
- adipose tissue
- high fat diet induced
- metabolic syndrome
- inflammatory response
- weight loss
- type diabetes
- oxidative stress
- soft tissue
- nuclear factor
- skeletal muscle
- body weight
- toll like receptor
- immune response
- mouse model
- lipopolysaccharide induced
- obese patients
- optical coherence tomography
- bariatric surgery
- high speed
- high resolution
- atomic force microscopy
- wild type