Research output: Contribution to journal › Article › Academic › peer-review
Chronic infusion of taurolithocholate into the brain increases fat oxidation in mice. / Eggink, Hannah M.; Tambyrajah, Lauren L.; van den Berg, Rosa et al.
In: Journal of endocrinology, Vol. 236, No. 2, 2018, p. 85-97.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Chronic infusion of taurolithocholate into the brain increases fat oxidation in mice
AU - Eggink, Hannah M.
AU - Tambyrajah, Lauren L.
AU - van den Berg, Rosa
AU - Mol, Isabel M.
AU - van den Heuvel, Jose K.
AU - Koehorst, Martijn
AU - Groen, Albert K.
AU - Boelen, Anita
AU - Kalsbeek, Andries
AU - Romijn, Johannes A.
AU - Rensen, Patrick C. N.
AU - Kooijman, Sander
AU - Soeters, Maarten R.
PY - 2018
Y1 - 2018
N2 - Bile acids can function in the postprandial state as circulating signaling molecules in the regulation of glucose and lipid metabolism via the transmembrane receptor TGR5 and nuclear receptor FXR. Both receptors are present in the central nervous system, but their function in the brain is unclear. Therefore, we investigated the effects of intracerebroventricular (i.c.v.) administration of taurolithocholate (tLCA), a strong TGR5 agonist, and GW4064, a synthetic FXR agonist, on energy metabolism. We determined the effects of chronic i.c.v. infusion of tLCA, GW4064, or vehicle on energy expenditure, body weight and composition as well as tissue specific fatty acid uptake in mice equipped with osmotic minipumps. We found that i.c.v. administration of tLCA (final concentration in cerebrospinal fluid: 1 mu M) increased fat oxidation (tLCA group: 0.083 +/- 0.006 vs control group: 0.036 +/- 0.023 kcal/h, F = 5.46, P = 0.04) and decreased fat mass (after 9 days of tLCA infusion: 1.35 +/- 0.13 vs controls: 1.96 +/- 0.23 g, P = 0.03). These changes were associated with enhanced uptake of triglyceride-derived fatty acids by brown adipose tissue and with browning of subcutaneous white adipose tissue. I.c.v. administration of GW4064 (final concentration in cerebrospinal fluid: 10 mu M) did not affect energy metabolism, body composition nor bile acid levels, negating a role of FXR in the central nervous system in metabolic control. In conclusion, bile acids such as tLCA may exert metabolic effects on fat metabolism via the brain
AB - Bile acids can function in the postprandial state as circulating signaling molecules in the regulation of glucose and lipid metabolism via the transmembrane receptor TGR5 and nuclear receptor FXR. Both receptors are present in the central nervous system, but their function in the brain is unclear. Therefore, we investigated the effects of intracerebroventricular (i.c.v.) administration of taurolithocholate (tLCA), a strong TGR5 agonist, and GW4064, a synthetic FXR agonist, on energy metabolism. We determined the effects of chronic i.c.v. infusion of tLCA, GW4064, or vehicle on energy expenditure, body weight and composition as well as tissue specific fatty acid uptake in mice equipped with osmotic minipumps. We found that i.c.v. administration of tLCA (final concentration in cerebrospinal fluid: 1 mu M) increased fat oxidation (tLCA group: 0.083 +/- 0.006 vs control group: 0.036 +/- 0.023 kcal/h, F = 5.46, P = 0.04) and decreased fat mass (after 9 days of tLCA infusion: 1.35 +/- 0.13 vs controls: 1.96 +/- 0.23 g, P = 0.03). These changes were associated with enhanced uptake of triglyceride-derived fatty acids by brown adipose tissue and with browning of subcutaneous white adipose tissue. I.c.v. administration of GW4064 (final concentration in cerebrospinal fluid: 10 mu M) did not affect energy metabolism, body composition nor bile acid levels, negating a role of FXR in the central nervous system in metabolic control. In conclusion, bile acids such as tLCA may exert metabolic effects on fat metabolism via the brain
U2 - 10.1530/JOE-17-0503
DO - 10.1530/JOE-17-0503
M3 - Article
C2 - 29233934
VL - 236
SP - 85
EP - 97
JO - Journal of endocrinology
JF - Journal of endocrinology
SN - 0022-0795
IS - 2
ER -
ID: 4437835