Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives

Juan P. Arab, Saul J. Karpen, Paul A. Dawson, Marco Arrese, Michael Trauner – 30 June 2016 – Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches to prevent disease progression to advanced fibrosis or cirrhosis and cancer.

Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice

Yang Xu, Fei Li, Munaf Zalzala, Jiesi Xu, Frank J. Gonzalez, Luciano Adorini, Yoon‐Kwang Lee, Liya Yin, Yanqiao Zhang – 30 June 2016 – Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption.

Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives

Juan P. Arab, Saul J. Karpen, Paul A. Dawson, Marco Arrese, Michael Trauner – 30 June 2016 – Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches to prevent disease progression to advanced fibrosis or cirrhosis and cancer.

Endothelial notch signaling is essential to prevent hepatic vascular malformations in mice

Henar Cuervo, Corinne M. Nielsen, Douglas A. Simonetto, Linda Ferrell, Vijay H. Shah, Rong A. Wang – 30 June 2016 – Liver vasculature is crucial for adequate hepatic functions. Global deletion of Notch signaling in mice results in liver vascular pathologies. However, whether Notch in endothelium is essential for hepatic vascular structure and function remains unknown. To uncover the function of endothelial Notch in the liver, we deleted Rbpj, a transcription factor mediating all canonical Notch signaling, or Notch1 from the endothelium of postnatal mice.

G‐protein‐coupled bile acid receptor plays a key role in bile acid metabolism and fasting‐induced hepatic steatosis in mice

Ajay C. Donepudi, Shannon Boehme, Feng Li, John Y.L. Chiang – 28 June 2016 – Bile acids are signaling molecules that play a critical role in regulation of hepatic metabolic homeostasis by activating nuclear farnesoid X receptor (Fxr) and membrane G‐protein‐coupled receptor (Takeda G‐protein‐coupled receptor 5; Tgr5). The role of FXR in regulation of bile acid synthesis and hepatic metabolism has been studied extensively. However, the role of TGR5 in hepatic metabolism has not been explored.

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