Carbenoxolone ameliorates hepatic lipid metabolism and inflammation in obese mice induced by high fat diet via regulating the JAK2/STAT3 signaling pathway

Abstract

Carbenoxolone (CBX) is the active principle of licorice, which is used to treat psoriasis, peptic ulcers, and wound healing. However, there is no report on how CBX ameliorates hepatic lipid metabolism and inflammation in obese mice. In this study, our aim is to explore the mechanism by which CBX regulates lipid metabolism in the liver of obese mice. C57BL/6J mice were divided into three groups and were fed with normal chow diet (NC group) or High-fat diet (HFD and CBX group) for eight weeks. Then mice in CBX group were given CBX every day by gavage for twelve weeks (15 mg/kg). Blood was collected for detection of triglycerides (TG), total cholesterol (TC), density lipoprotein (LDL), high-density lipoprotein (HDL), Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST). Liver tissues were stained with hematoxylin-eosin for histological examination. Immunohistochemical staining was performed for detection of SOCS-3 (Suppressor of cytokine signaling 3), SREBP-1 (Sterol regulatory element-binding protein 1), and FAS (Fatty acid synthase) protein. The genes of SOCS-3, SREBP-1, and FAS in liver were assessed by real-time PCR. Western blotting was applied to detect the protein expressions of the phosphorylated JAK2 (Janus kinase 2) and phosphorylated STAT3 (Signal transducer and activator of transcription 3). Our results showed that compared with the HFD group, serum concentrations of TG, TC and LDL were decreased significantly, while the concentration of HDL was increased in the CBX group. CBX could attenuate intracellular lipid accumulation in the liver. Besides, treatment with CBX could significantly decrease levels of inflammatory factors such as IL-6 (Interleukin 6) and TNF-a (Tumor necrosis factor-a), increase expressions of phosphorylated JAK2 and phosphorylated STAT3, decrease the expressions of SOCS-3, SREBP-1 and FAS in the liver. In conclusion, through activating the JAK2/STAT3 signaling pathway in liver and reducing the expression of SCOCS-3, CBX could further decrease the expressions of SREBP-1c, FAS and ameliorate the inflammatory state of liver, so as to protecting the liver from lipid metabolism damage induced by high-fat diet. Therefore, CBX has the possibility for the treatment of obesity, hyperlipidemia, and inflammation.