OBJECTIVES: Metabolic syndrome (MS) is the concurrence of at least three of five medical conditions: obesity, high blood pressure, insulin resistance, high serum triglyceride (TG) and low serum high-density lipoprotein levels. While fibrates are used to treat disorders other than the lowering serum TG, the mechanism by which fibrates decrease MS has not been established. METHODS: In this study, wild-type and Ppara-null mice fed a medium-fat diet (MFD) were administered gemfibrozil and fenofibrate for 3 months respectively, to explore the effect and action mechanism. KEY FINDINGS: In Ppara-null mice, MFD treatment increased body weight, adipose tissue, serum TG and impaired glucose tolerance. These phenotypes were attenuated in two groups treated with gemfibrozil and fenofibrate. The STAT3 pathway was activated in adipose and hepatic tissues in positive control, and inhibited in groups treated with gemfibrozil and fenofibrate. The above phenotypes and inflammation were not observed in any wild-type group. In 3T3-L1 adipogenic stem cells treated with high glucose, STAT3 knockdown greatly decreased the number of lipid droplets. CONCLUSIONS: Low dose of clinical fibrates was effective against MS development independent of PPARα, and this action was mediated by STAT3 signalling inhibition in adipose tissue and, to a lesser extent, in hepatic tissues.
OBJECTIVES:Metabolic syndrome (MS) is the concurrence of at least three of five medical conditions: obesity, high blood pressure, insulin resistance, high serum triglyceride (TG) and low serum high-density lipoprotein levels. While fibrates are used to treat disorders other than the lowering serum TG, the mechanism by which fibrates decrease MS has not been established. METHODS: In this study, wild-type and Ppara-null mice fed a medium-fat diet (MFD) were administered gemfibrozil and fenofibrate for 3 months respectively, to explore the effect and action mechanism. KEY FINDINGS: In Ppara-null mice, MFD treatment increased body weight, adipose tissue, serum TG and impaired glucose tolerance. These phenotypes were attenuated in two groups treated with gemfibrozil and fenofibrate. The STAT3 pathway was activated in adipose and hepatic tissues in positive control, and inhibited in groups treated with gemfibrozil and fenofibrate. The above phenotypes and inflammation were not observed in any wild-type group. In 3T3-L1 adipogenic stem cells treated with high glucose, STAT3 knockdown greatly decreased the number of lipid droplets. CONCLUSIONS: Low dose of clinical fibrates was effective against MS development independent of PPARα, and this action was mediated by STAT3 signalling inhibition in adipose tissue and, to a lesser extent, in hepatic tissues.
Authors: K Tordjman; C Bernal-Mizrachi; L Zemany; S Weng; C Feng; F Zhang; T C Leone; T Coleman; D P Kelly; C F Semenkovich Journal: J Clin Invest Date: 2001-04 Impact factor: 14.808
Authors: Qian Gao; Michael J Wolfgang; Susanne Neschen; Katsutaro Morino; Tamas L Horvath; Gerald I Shulman; Xin-Yuan Fu Journal: Proc Natl Acad Sci U S A Date: 2004-03-22 Impact factor: 11.205
Authors: Marcia L E MacDonald; Miranda van Eck; Reeni B Hildebrand; Brian W C Wong; Nagat Bissada; Piers Ruddle; Anatol Kontush; Hala Hussein; Mahmoud A Pouladi; M John Chapman; Catherine Fievet; Theo J C van Berkel; Bart Staels; Bruce M McManus; Michael R Hayden Journal: Arterioscler Thromb Vasc Biol Date: 2008-12-18 Impact factor: 8.311