A translational view on the biliary lipid secretory network

Bile formation springs from an extraordinary sophisticated secretory network, which combines the activity of transport proteins with the physico-chemical properties of small albeit powerful lipophilic compounds. This robust interplay is activated in response to dietary stimuli, circadian rhythms, and metabolic demands to regulate cholesterol disposal, lipid digestion and absorption in the enterohepatic system. As a result, bile flow is a complex multi-organ effort that requires an integrated flux of information between liver and intestine. A coordinate regulatory task is achieved by nuclear receptors, which are ligand activated transcription factors, responsible for the coherent activation of sets of genes involved in multiple physiological actions, including hepato-biliary homeostasis. Mastering the molecular pathways underlying functional and pharmacological modulation of bile flow has great translational value for potential future treatment of cholestasis and cholelithiasis. In this review, we focus on recent discoveries in the functional biology of bile formation with the explicit aim of underlining their putative clinical relevance.