title: A novel animal model of metabolic syndrome with non-alcoholic fatty liver disease and skin inflammation.
abstract: BACKGROUND
  Metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) are the emerging co-morbidities of skin inflammation. Occurrence of skin inflammation such as psoriasis is substantially higher in NAFLD patients than normal. Currently, there are no animal models to study the interaction between these co-morbidities.
  
  
  OBJECTIVE
  The present study seeks to develop a simple mouse model of NAFLD-enhanced skin inflammation and to study the effect of NAFLD on different parameters of skin inflammation.
  
  
  METHODS
  Metabolic syndrome and NAFLD were induced in C57BL/6 mice by feeding high-fat diet (HFD, 60% kcal) and high fructose liquid (HFL, 40% kcal) in drinking water. Skin inflammation was induced by repeated application of oxazolone (1% sensitization and repeated 0.5% challenge) in both normal and NAFLD mice and various parameters of skin inflammation and NAFLD were measured.
  
  
  RESULTS
  HFD and HFL diet induced obesity, hyperglycemia, hyperinsulinemia, and histological features of NAFLD in mice. Oxazolone challenge significantly increased ear thickness, ear weight, MPO activity, NF-κB activity, and histological features of skin inflammation in NAFLD mice as compared with normal mice. Overall, induction of oxazolone-induced skin inflammation was more prominent in NAFLD mice than normal mice. Hence, HFD and HFL diet followed by topical oxazolone application develops metabolic syndrome, NAFLD, and enhanced skin inflammation in mice.
  
  
  CONCLUSIONS
  This simple model can be utilized to evaluate a therapeutic strategy for the treatment of metabolic syndrome and NAFLD with skin inflammation and also to understand the nexus between these co-morbidities.
authors.affiliation: Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd. , Chennai, Tamil Nadu , India and.
authors.forename: Nagaraj M
authors.initials: NM
authors.lastname: Kulkarni
authors.forename: Mallikarjun S
authors.initials: MS
authors.lastname: Jaji
authors.forename: Pranesha
authors.initials: P
authors.lastname: Shetty
authors.forename: Yeshwant V
authors.initials: YV
authors.lastname: Kurhe
authors.forename: Shilpee
authors.initials: S
authors.lastname: Chaudhary
authors.forename: G
authors.initials: G
authors.lastname: Vijaykant
authors.forename: J
authors.initials: J
authors.lastname: Raghul
authors.forename: Santosh L
authors.initials: SL
authors.lastname: Vishwakarma
authors.forename: B Navin
authors.initials: BN
authors.lastname: Rajesh
authors.forename: Jeyamurugan
authors.initials: J
authors.lastname: Mookkan
authors.forename: Uma Maheswari
authors.initials: UM
authors.lastname: Krishnan
authors.forename: Shridhar
authors.initials: S
authors.lastname: Narayanan
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology
keywords: Animal model; metabolic syndrome; non-alcoholic fatty liver disease (NAFLD); nuclear factor-kappa B; oxazolone; skin inflammation