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Bile acid alterations in nonalcoholic fatty liver disease, obesity, insulin resistance and type 2 diabetes

what do the human studies tell?

Chávez-Talavera, Oscar*; Haas, Joel*; Grzych, Guillaume; Tailleux, Anne; Staels, Bart

Current Opinion in Lipidology: June 2019 - Volume 30 - Issue 3 - p 244–254
doi: 10.1097/MOL.0000000000000597
LIPID METABOLISM: Edited by Marit Westerterp and Bart van de Sluis
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Purpose of review The purpose of this review is to discuss the influence of obesity, insulin resistance, type 2 diabetes (T2D), and nonalcoholic fatty liver disease (NAFLD) on bile acid metabolism and to analyze whether these findings reinforce current beliefs about the role of bile acids in the pathophysiology of these diseases.

Recent findings Discordant results on plasma bile acid alterations in NAFLD patients have been reported. Obesity, insulin resistance, and T2D, common comorbidities of NAFLD, have been associated with bile acid changes, but the individual bile acid species variations differ between studies (summarized in this review), perhaps because of clinicobiological differences between the studied patient populations and the heterogeneity of statistical analyses applied.

Summary The regulatory role of bile acids in metabolic and cellular homeostasis renders bile acids attractive candidates as players in the pathophysiology of NAFLD. However, considering the complex relationship between NAFLD, obesity, insulin resistance and T2D, it is difficult to establish clear and independent associations between bile acid alterations and these individual diseases. Though bile acid alterations may not drive NAFLD progression, signaling pathways activated by bile acids remain potent therapeutic targets for its treatment. Further studies with appropriate matching or adjustment for potential confounding factors are necessary to determine which pathophysiological conditions drive the alterations in bile acid metabolism.

University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, F-59000 Lille, France

Correspondence to Bart Staels, Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP245, 59019 Lille, France. Tel: +33320877388; fax: +33320877360; e-mail: bart.staels@pasteur-lille.fr

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