Identification of fibroblast growth factor 15 as a novel mediator of liver regeneration and its application in the prevention of post-resection liver failure in mice

Uriarte, Iker; Fernández‐Barrena, Maite G.; Monte, María J.; Latasa, María U.; Chang, Haisul C Y; Carotti, Simone; Gentilucci, Umberto Vespasiani; Morini, Sergio; Vicente, Eva; Concepcion, Axel R.; Medina, Juan F.; Marin, José J.G.; Berasain, Carmen; Prieto, Jesús; Avila, Matı́as A.

doi:10.1136/gutjnl-2012-302945

Cited by 165 publications

(252 citation statements)

References 56 publications

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“…FGF19 travels in portal venous blood to the liver and downregulates bile acid biosynthesis ( 55,56 ). FGF19 promotes hepatocyte growth ( 57 ), and FXR agonism also has antidiabetic effects mediated by multiple mechanisms ( 58 ), as well as anti-infl ammatory being the helical structure of DNA and RNA by Watson and Crick. Bernal's left wing political views and his Bohemian life style probably kept him from being awarded a Nobel Prize ( 89,90 ).…”

Section: History Of Bile Acid Researchmentioning

confidence: 99%

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Hofmann

Hagey

2014

Journal of Lipid Research

297

284

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conceptions are rare, and provocative judgments stand the test of time. Let us also hope that this effort will be both useful and entertaining. Each of the topics discussed merits at least a full length article, so there will be, of necessity in many instances, consideration of only what we perceive to be the highlights. THE EBB AND FLOW OF MEDICAL INTEREST IN BILE ACIDSAfter the elucidation of the true chemical structure of bile acids in 1932 (see below), there was little interest in bile acids in the Western world. One exception to this statement was the laboratory of Siegfried Thannhauser, who wrote the fi rst textbook of metabolic biochemistry in Germany. He studied cholesterol and bile acid balance in the biliary fi stula dog ( 1 ). During this time, bile acids were sold as liver tonics and laxatives, but there were no placebo-controlled studies showing effi cacy. Indeed, bile acids were considered by the medical profession to have no useful therapeutic properties. The tri-oxo derivative of cholic acid (called "dehydrocholic acid") was known to induce bile fl ow in animals ( 2 ), and was occasionally used to stimulate bile fl ow in patients; but again there were no controlled studies showing effi cacy in hepatobiliary disease.

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Section: History Of Bile Acid Researchmentioning

confidence: 99%

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Hofmann

Hagey

2014

Journal of Lipid Research

297

284

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“…Moreover, a delicate intrahepatic balance of bile salts is needed for proper liver regeneration as shown in animal studies. 34 It may be worthwhile to explore the prognostic potential of bile salts in PLF. Although the clinical characteristics of the present study resemble those of the cohort of Mullen et al, some dissimilarities were present.…”

Section: Discussionmentioning

confidence: 99%

Validation of the peak bilirubin criterion for outcome after partial hepatectomy

Mierlo

Lodewick

Dhar

et al. 2016

HPB

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“…Following PHx in rodents, an increase in systemic bile salts is detectable already after 1 min and levels reach a peak during the first 24 h [26,[31][32][33][34]. This rapid incline is likely due to hemodynamic alterations exposing the remnant liver to a relative bile salt overload [33].…”

Section: Bile Salts and Liver Regenerationmentioning

confidence: 99%

“…Both intestinal and liver Fxr are required for normal liver regeneration after PHx, thus, ensuring Fgf15 appears to serve a double role in liver regeneration through effects on bile salt homeostasis and by acting as a mitogen for hepatocytes and cholangioytes [25]. PHx in Fgf15 knockout mice results in higher mortality than in mice lacking Fxr [26,32,49]. The hepatic expression of the Fgf15/FGF19 receptor Fgfr4 increases after PHx [50].…”

Section: Farnesoid X Receptor and Liver Regenerationmentioning

confidence: 99%

“…The liver-to-body weight ratio was only mildly reduced in hepatectomized Fgfr4 -/-mice as a result of cellular hypertrophy that compensated reduced hyperplasia [51]. The survival of mice after extended liver resection (85 % PHx, a surgical model for acute liver failure) can be improved by exogenous administration of Fgf15 [32].…”

Section: Farnesoid X Receptor and Liver Regenerationmentioning

confidence: 99%

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The role of bile salts in liver regeneration

et al. 2016

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A growing body of evidence has demonstrated that bile salts are important for liver regeneration following partial hepatectomy. The relative bile salt overload after partial liver resection causes activation of bile salt receptors in non-parenchymal (viz. the plasma membrane receptor TGR5) and parenchymal (viz. the intracellular receptor FXR) cells in the liver, thus, providing signals to the regenerative process. Impaired bile salt signaling in mice with genetic deficiency of Tgr5 or Fxr results in delayed liver regeneration after partial hepatectomy, and is accompanied by mortality in case of Fxr knock-out mice. Conversely, compensatory liver re-growth in hepatectomized mice can be stimulated by feeding of bile salts or alisol B 23-acetate, a natural triterpenoid agonist of Fxr. A large number of animal studies underscore the importance of strict maintenance of bile salt homeostasis for proper progression of liver regeneration. Both ileal and hepatic Fxr play a key role in regulation of bile salt homeostasis and, thus, preventing hepatotoxicity caused by excessive levels of bile salts. They further contribute to liver regeneration by induction of mitogenic factors. Agents that target bile salt receptors hold promise as drugs to stimulate liver regeneration in selected patients.

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Identification of fibroblast growth factor 15 as a novel mediator of liver regeneration and its application in the prevention of post-resection liver failure in mice

Cited by 165 publications

References 56 publications

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

Validation of the peak bilirubin criterion for outcome after partial hepatectomy

The role of bile salts in liver regeneration

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