Marleen Schonewille1, Jan Freark de Boer, Albert K Groen. 1. aDepartment of Pediatrics bDepartment of Laboratory Medicine, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen cAmsterdam Diabetes Center, Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands *Marleen Schonewille and Jan Freark de Boer contributed equally to the writing of this article.
Abstract
PURPOSE OF REVIEW: The view on bile salts has evolved over the years from being regarded as simple detergents that aid intestinal absorption of fat-soluble nutrients to being important hormone-like integrators of metabolism. This review provides an update on the rapidly developing field of interactions between bile salts and lipid metabolism, with a particular emphasis on the underlying mechanisms. RECENT FINDINGS: The nuclear receptor farnesoid X receptor (FXR) plays major roles in bile salt-mediated signaling pathways. The recent identification of novel FXR targets and factors involved in FXR signaling highlights the interactions of bile acids with lipid metabolism. Exciting data have been reported on the use of intestine-specific FXR agonists as well as antagonists. In addition, encouraging results for treatment of hepatic steatosis obtained with obeticholic acid in the FLINT trial underline the therapeutic potential of bile salt signaling and metabolism for the treatment of lipid disorders. SUMMARY: Modulation of FXR activity appears to be a potent target, not only for improving bile salt homeostasis, but also to improve lipid metabolism. Depending on the metabolic context both, FXR agonists as well as antagonists, could prove to be of therapeutic benefit.
PURPOSE OF REVIEW: The view on bile salts has evolved over the years from being regarded as simple detergents that aid intestinal absorption of fat-soluble nutrients to being important hormone-like integrators of metabolism. This review provides an update on the rapidly developing field of interactions between bile salts and lipid metabolism, with a particular emphasis on the underlying mechanisms. RECENT FINDINGS: The nuclear receptor farnesoid X receptor (FXR) plays major roles in bile salt-mediated signaling pathways. The recent identification of novel FXR targets and factors involved in FXR signaling highlights the interactions of bile acids with lipid metabolism. Exciting data have been reported on the use of intestine-specific FXR agonists as well as antagonists. In addition, encouraging results for treatment of hepatic steatosis obtained with obeticholic acid in the FLINT trial underline the therapeutic potential of bile salt signaling and metabolism for the treatment of lipid disorders. SUMMARY: Modulation of FXR activity appears to be a potent target, not only for improving bile salt homeostasis, but also to improve lipid metabolism. Depending on the metabolic context both, FXR agonists as well as antagonists, could prove to be of therapeutic benefit.
Authors: Stephanie J Shiffka; Jace W Jones; Linhao Li; Ann M Farese; Thomas J MacVittie; Hongbing Wang; Peter W Swaan; Maureen A Kane Journal: J Lipid Res Date: 2020-07-22 Impact factor: 5.922
Authors: Svenja Sydor; Jan Best; Insa Messerschmidt; Paul Manka; Ramiro Vilchez-Vargas; Susanne Brodesser; Christina Lucas; Annemarie Wegehaupt; Chiara Wenning; Sophia Aßmuth; Simon Hohenester; Alexander Link; Klaas Nico Faber; Han Moshage; Francisco Javier Cubero; Scott L Friedman; Guido Gerken; Michael Trauner; Ali Canbay; Lars P Bechmann Journal: Clin Transl Gastroenterol Date: 2020-03 Impact factor: 4.396