title: Tesaglitazar ameliorates non-alcoholic fatty liver disease and atherosclerosis development in diabetic low-density lipoprotein receptor-deficient mice.
abstract: Previous research has demonstrated that the dual PPARα/γ agonist tesaglitazar reduces atherosclerosis in a mouse model of hyperlipidemia by reducing both lipid content and inflammation in the aorta. However, much of the underlying mechanism of tesaglitazar in non-alcoholic fatty liver disease (NAFLD) remains less clear. The aim of the present study was to determine whether tesaglitazar attenuates NAFLD and atherosclerosis development in diabetic low-density lipoprotein receptor-deficient (LDLr(-/-)) mice. Female LDLr(-/-) mice (3 weeks old) were induced by a high-fat diet (HFD) combined with low-dose streptozotocin (STZ) injection to develop an animal model of type 2 diabetes (T2DM). The mice were randomly divided into two groups: diabetic group (untreated diabetic mice, n=15) and tesaglitazar therapeutic group (n=15, 20 μg/kg/day oral treatment for 6 weeks). Fifteen LDLr(-/-) mice were fed with an HFD as the control group. Tesaglitazar decreased serum glucose and lipid levels compared with the diabetic mice. Tesaglitazar significantly reduced atherosclerotic lesions, lipid accumulation in the liver, macrophage infiltration, and decreased total hepatic cholesterol and triglyceride content compared to the diabetic mice. In addition, tesaglitazar reduced inflammatory markers at both the serum and mRNA levels. Our data suggest that tesaglitazar may be effective in preventing NAFLD and atherosclerosis in a pre-existing diabetic condition by regulating glucose and lipid metabolism, and the inflammatory response.
authors.affiliation: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072,  P.R. China.
authors.forename: Bu-Chun
authors.initials: BC
authors.lastname: Zhang
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Li
authors.forename: Xian-Kai
authors.initials: XK
authors.lastname: Li
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Zhu
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Che
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Xu