The emerging role of bile acids in white adipose tissue.

Bile acids (BAs) in the peripheral circulation represent a specific but underestimated physiological compartment Systemic (peripheral) BAs can be regarded as specific steroidal hormones that act on white adipocytes. The term 'bilokines' ('bile hormones') is suggested for peripheral BAs subspecies acting on specific receptors on adipocytes and peripheral tissues other than gut or liver. Adipoflammation and metaflammation in visceral obesity represent the main and causal mechanisms for insulin resistance and type 2 diabetes mellitus (T2D), and can be targeted by BAs in an anti-inflammatory manner. The kinetics of systemic BA subspecies upon feeding and bariatric surgery represents a widely uncharacterized black box whose decipherment could help to identify single BAs as druggable targets in obesity, T2D, and metabolic syndrome. The effects of bile acids (BAs) on liver, enteroendocrine function, small intestine, and brown adipose tissue have been described extensively. Outside the liver, BAs in the peripheral circulation system represent a specific but underappreciated physiological compartment. We discuss how systemic BAs can be regarded as specific steroidal hormones that act on white adipocytes, and suggest the name 'bilokines' ('bile hormones') for the specific FXR/TGR5 receptor interaction in adipocytes. Some BAs and their agonists regulate adipocyte differentiation, lipid accumulation, hypoxia, autophagy, adipokine and cytokine secretion, insulin signaling, and glucose uptake. BA signaling could provide a new therapeutic avenue for adipoflammation and metaflammation in visceral obesity, the causal mechanisms underlying insulin resistance and type 2 diabetes mellitus (T2D). [ABSTRACT FROM AUTHOR]