scholarly journals Forced expression of fibroblast growth factor 21 reverses the sustained impairment of liver regeneration in hPPARαPAC mice due to dysregulated bile acid synthesis

Oncotarget ◽  
2015 ◽  
Vol 6 (12) ◽  
pp. 9686-9700 ◽  
Author(s):  
Hui-Xin Liu ◽  
Ying Hu ◽  
Samuel W. French ◽  
Frank J. Gonzalez ◽  
Yu-Jui Yvonne Wan
Keyword(s):  
Bile Acid ◽  
Growth Factor ◽  
Liver Regeneration ◽  
Fibroblast Growth Factor ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

scholarly journals Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19

2015 ◽  
Vol 14 (5) ◽  
pp. 710-721 ◽  
Author(s):  
Francisco Barrera ◽  
Lorena Azocar ◽  
Héctor Molina ◽  
Kurt A. Schalper ◽  
Marcia Ocares ◽  
...  
Keyword(s):  
Bile Acid ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor 19 ◽  
Circulating Levels

scholarly journals Fibroblast Growth Factor Receptor 4 (FGFR4) Deficiency Improves Insulin Resistance and Glucose Metabolism under Diet-induced Obesity Conditions

2014 ◽  
Vol 289 (44) ◽  
pp. 30470-30480 ◽  
Author(s):  
Hongfei Ge ◽  
Jun Zhang ◽  
Yan Gong ◽  
Jamila Gupte ◽  
Jay Ye ◽  
...  
Keyword(s):  
Bile Acid ◽  
Growth Factor ◽  
Glucose Metabolism ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Fibroblast Growth ◽  
Bile Acid Receptors

The role of fibroblast growth factor receptor 4 (FGFR4) in regulating bile acid synthesis has been well defined; however, its reported role on glucose and energy metabolism remains unresolved. Here, we show that FGFR4 deficiency in mice leads to improvement in glucose metabolism, insulin sensitivity, and reduction in body weight under high fat conditions. Mechanism of action studies in FGFR4-deficient mice suggest that the effects are mediated in part by increased plasma levels of adiponectin and the endocrine FGF factors FGF21 and FGF15, the latter of which increase in response to an elevated bile acid pool. Direct actions of increased bile acids on bile acid receptors, and other potential indirect mechanisms, may also contribute to the observed metabolic changes. The results described herein suggest that FGFR4 antagonists alone, or in combination with other agents, could serve as a novel treatment for diabetes.

scholarly journals Diet1 Is a Regulator of Fibroblast Growth Factor 15/19-Dependent Bile Acid Synthesis

2015 ◽  
Vol 33 (3) ◽  
pp. 307-313 ◽  
Author(s):  
Karen Reue ◽  
Jessica M. Lee ◽  
Laurent Vergnes
Keyword(s):  
Bile Acid ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Control Point ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Acid Uptake ◽  
Fibroblast Growth ◽  
Hepatic Bile ◽  
Bile Acid Uptake

Background: A fascinating aspect of bile acid homeostasis is the coordination between bile acid uptake in intestine and hepatic bile acid synthesis. In response to bile acid uptake in enterocytes, farnesoid X receptor is activated and induces transcription of fibroblast growth factor (FGF)15 in mice, or FGF19 in humans. FGF15/19 is secreted into the enterohepatic circulation, and through activation of hepatic receptors, leads to repression of Cyp7a1, a rate-limiting enzyme for bile acid synthesis. Using a genetic approach, we identified a novel protein, Diet1, as a control point for FGF15/19 production. Key Messages: Mice with a Diet1-null mutation have reduced FGF15 secretion, causing impaired feedback repression of hepatic bile acid synthesis, and increased fecal bile acid excretion. As a result, Diet1-deficient mice constitutively convert cholesterol to bile acids and are resistant to diet-induced hypercholesterolemia and atherosclerosis. Diet1 affects FGF15/19 production at the posttranscriptional level, and the proteins appear to have overlapping subcellular localization in enterocytes. Diet1 appears to be a control point for the production of FGF15/19 in enterocytes, and thus a regulator of bile acid and lipid homeostasis. Studies to evaluate the role of common and rare DIET1 genetic variants in human health and disease are warranted. Conclusions: Further elucidation of the Diet1-FGF15/19 interaction will provide new insights into the intricate regulatory mechanisms underlying bile acid metabolism.

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