Kulkarni Nagaraj M, Jaji Mallikarjun S, Shetty Pranesha, Kurhe Yeshwant V, Chaudhary Shilpee, Vijaykant G, Raghul J, Vishwakarma Santosh L, Rajesh B Navin, Mookkan Jeyamurugan, Krishnan Uma Maheswari, Narayanan Shridhar
Department of Biology, Drug Discovery Research, Orchid Chemicals and Pharmaceuticals Ltd. , Chennai, Tamil Nadu , India and.
Pharm Biol. 2015 Aug;53(8):1110-7. doi: 10.3109/13880209.2014.960944. Epub 2014 Nov 28.
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.
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.
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.
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.
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.
代谢综合征和非酒精性脂肪性肝病(NAFLD)是新出现的与皮肤炎症相关的共病。NAFLD患者中银屑病等皮肤炎症的发生率显著高于正常人。目前,尚无用于研究这些共病之间相互作用的动物模型。
本研究旨在建立一种简单的NAFLD增强皮肤炎症的小鼠模型,并研究NAFLD对皮肤炎症不同参数的影响。
通过给C57BL/6小鼠喂食高脂饮食(HFD,60%千卡)和饮用含高果糖液体(HFL,40%千卡)诱导代谢综合征和NAFLD。在正常小鼠和NAFLD小鼠中通过反复涂抹恶唑酮(1%致敏和反复0.5%激发)诱导皮肤炎症,并测量皮肤炎症和NAFLD的各种参数。
HFD和HFL饮食诱导小鼠肥胖、高血糖、高胰岛素血症以及NAFLD的组织学特征。与正常小鼠相比,恶唑酮激发显著增加了NAFLD小鼠的耳厚度、耳重量、MPO活性、NF-κB活性以及皮肤炎症的组织学特征。总体而言,恶唑酮诱导的皮肤炎症在NAFLD小鼠中比正常小鼠更明显。因此,HFD和HFL饮食后局部应用恶唑酮可在小鼠中引发代谢综合征、NAFLD和增强的皮肤炎症。
这个简单的模型可用于评估治疗伴有皮肤炎症的代谢综合征和NAFLD的治疗策略,也有助于理解这些共病之间的联系。