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Xiong X.,Shanghai JiaoTong University | Wang X.,Shanghai JiaoTong University | Lu Y.,Shanghai JiaoTong University | Wang E.,Shanghai JiaoTong University | And 5 more authors.
Journal of Hepatology | Year: 2014

Background & Aims Non-alcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride (TG) contents. The prevalence of NAFLD is increased with aging. However, the molecular mechanism for aging-induced fatty liver remains poorly understood. Methods Hepatic TG contents and gene expression profiles were analyzed in body weight-matched young (2 months), middle (8 months) and old (18 months) C57BL/6 mice. Endoplasmic reticulum (ER) stress and farnesoid X receptor (FXR) expression were examined. The mechanism of ER stress activation in the regulation of FXR expression was further investigated. Results In the present study, we found that TG was markedly accumulated and lipogenic genes were up-regulated in the liver of C57BL/6 mice aged 18 months. FXR, a key regulator of hepatic lipid metabolism was down-regulated in these old mice. At molecular levels, ER stress was activated in old mice and repressed FXR expression through inhibition of hepatocyte nuclear factor 1 alpha (HNF1α) transcriptional activity. Conclusions Our findings demonstrate that FXR down-regulation plays a critical role in aging-induced fatty liver. © 2013 European Association for the Study of the Liver. Published. Source

Jiao Y.,Shanghai JiaoTong University | Lu Y.,Shanghai JiaoTong University | Li X.-Y.,Shanghai JiaoTong University | Li X.-Y.,stitute of Shanghai Universities
Acta Pharmacologica Sinica | Year: 2015

Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia. © 2015 CPS and SIMM. Source

Li L.,Institute of Cardiology | Chen G.-P.,Institute of Cardiology | Yang Y.,Institute of Cardiology | Ye Y.,Institute of Cardiology | And 3 more authors.
Biochemical Pharmacology | Year: 2010

Farnesyl pyrophosphate synthase (FPPS), an essential enzyme in the mevalonate pathway, was reported to be upregulated in young spontaneously hypertensive rats (SHR) when compared with Wistar-Kyoto (WKY) rats, and this was accompanied by development of left ventricular hypertrophy. Five-week-old rats were daily gavaged with vehicle or an FPPS inhibitor (alendronate, 1 or 10 mg/kg) and blood pressures was monitored by the tail-cuff method every other week. Twelve weeks of alendronate treatment attenuated the left ventricular weight to body weight ratio (LVW/BW), hydroxyproline content, collagen deposition in the interstitia, and gene expression of atrial natriuretic peptide, B-type natriuretic peptide, and procollagen type I/III in the SHR left ventricle, all of which were significantly higher in SHRs than in WKY rats. Furthermore, long-term treatment with an FPPS inhibitor significantly reduced RhoA activation, ERK phosphorylation, and TGF-β1 expression in the SHR left ventricle, all of which were upregulated more in SHRs than in WKY rats. In conclusion, chronic treatment with an FPPS inhibitor attenuates the development of cardiac hypertrophy and fibrosis, and the suppression of ERK1/2 phosphorylation and TGF-β1 expression with inhibition of RhoA activation may be an important mechanism. © 2009. Source

Wang N.,Shanghai Institute of Technology | Ni M.,East China Normal University | Ni M.,stitute of Shanghai Universities
Acta Mathematica Scientia | Year: 2013

In this article, we study a kind of vector singularly perturbed delay-differential equation. Using boundary layer function method and geometric analysis skill, the asymptotic expression of the system is constructed and the uniform validity of asymptotic solution is also proved. © 2013 Wuhan Institute of Physics and Mathematics. Source

Wang T.,Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health | Wang T.,Shanghai JiaoTong University | Wang T.,stitute of Shanghai Universities | Ning G.,Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health | And 3 more authors.
Journal of Diabetes | Year: 2013

Diabetes and cancer are both heterogeneous and multifactorial diseases with tremendous impact on health worldwide. Epidemiologic evidence suggests that certain malignancies may be associated with diabetes, as well as with diabetes risk factors and, perhaps, with certain diabetes treatments. Numerous biological mechanisms could account for these relationships. Insulin-like growth factor (IGF)-1, IGF-2, IGF-1 receptors, insulin, and the insulin receptor play roles in the development and progression of cancers. Although evidence from randomized controlled trials does not support or refute associations of diabetes and its treatments with either increased or reduced risk of cancer incidence or prognosis, consideration of malignancy incidence rates and the magnitude of the trials that would be required to address these issues explains why such studies may not be readily undertaken. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd. Source

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