Fig. 2
From: Roles of bile acids signaling in neuromodulation under physiological and pathological conditions
Bile acids signal to the central nervous system (CNS). Bile acids (BA) in the intestinal lumen can signal to the CNS via the direct pathway or indirect pathway. Bile acids in the intestine escape the enterohepatic circulation, reach the systemic circulation, and cross the blood-brain barrier (BBB) to interact with receptors in the brain. BA in the CNS could exert an anorexigenic effect via activating TGR5 in the hypothalamic arcuate nucleus or block GABAA receptor on tuberomammillary nucleus (TMN) of the hypothalamus to promote wakefulness. BA taken up by enterocytes can activate the nuclear receptor FXR to promote FGF15/19 production. FGF15/19 is released by the enterocytes, enters the systemic circulation, and cross the BBB to interact with FGF receptors in the brain. The central effects of FGF15/19 are involved in glucose metabolism and energy homeostasis. TGR5 activation by BA in enteroendocrine L-cells triggers GLP-1 production. GLP-1 could interact with GLP-1 receptors expressed on afferent terminals of the vagal nerve present in the lamina propria and portal vein. The vagal nerve projects to the brainstem, from where projections are further directed toward other brain regions. GLP-1 is believed to exert its inhibitory effect on food intake and energy homeostasis via the vagal-brainstem-hypothalamic pathway