Chronic infusion of taurolithocholate into the brain increases fat oxidation in mice.

Autor:	Eggink HM; Department of Endocrinology and MetabolismAcademic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.; Hypothalamic Integration MechanismsNetherlands Institute for Neuroscience, Amsterdam, The Netherlands., Tambyrajah LL; Division of EndocrinologyDepartment of Medicine, Leiden University Medical Centre, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical Centre, Leiden, The Netherlands., van den Berg R; Division of EndocrinologyDepartment of Medicine, Leiden University Medical Centre, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical Centre, Leiden, The Netherlands., Mol IM; Division of EndocrinologyDepartment of Medicine, Leiden University Medical Centre, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical Centre, Leiden, The Netherlands., van den Heuvel JK; Division of EndocrinologyDepartment of Medicine, Leiden University Medical Centre, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical Centre, Leiden, The Netherlands., Koehorst M; Department of Pediatrics and Laboratory MedicineUniversity Medical Centre Groningen, University of Groningen, Groningen, The Netherlands., Groen AK; Department of Pediatrics and Laboratory MedicineUniversity Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.; Department of Vascular MedicineAmsterdam Diabetes Centre, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Boelen A; Department of Endocrinology and MetabolismAcademic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Kalsbeek A; Department of Endocrinology and MetabolismAcademic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.; Hypothalamic Integration MechanismsNetherlands Institute for Neuroscience, Amsterdam, The Netherlands., Romijn JA; Department of MedicineAcademic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands., Rensen PCN; Division of EndocrinologyDepartment of Medicine, Leiden University Medical Centre, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical Centre, Leiden, The Netherlands., Kooijman S; Division of EndocrinologyDepartment of Medicine, Leiden University Medical Centre, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical Centre, Leiden, The Netherlands., Soeters MR; Department of Endocrinology and MetabolismAcademic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands m.r.soeters@amc.uva.nl.
Jazyk:	angličtina
Zdroj:	The Journal of endocrinology [J Endocrinol] 2018 Feb; Vol. 236 (2), pp. 85-97. Date of Electronic Publication: 2017 Dec 12.
DOI:	10.1530/JOE-17-0503
Abstrakt:	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 μM) 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 μM) 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. (© 2018 Society for Endocrinology.)
Databáze:	MEDLINE
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