FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues.

Autor:	Schlein C; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany., Talukdar S; Cardiovascular Metabolic and Endocrine Diseases (CVMED), Pfizer, 610 Main Street, Cambridge, MA 02139, USA., Heine M; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany., Fischer AW; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany., Krott LM; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany., Nilsson SK; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany., Brenner MB; Cardiovascular Metabolic and Endocrine Diseases (CVMED), Pfizer, 610 Main Street, Cambridge, MA 02139, USA., Heeren J; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany., Scheja L; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: l.scheja@uke.de.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2016 Mar 08; Vol. 23 (3), pp. 441-53. Date of Electronic Publication: 2016 Feb 04.
DOI:	10.1016/j.cmet.2016.01.006
Abstrakt:	FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, we examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice. Treatment with pharmacological doses of FGF21 acutely reduced plasma non-esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues. Insulin resistance in diet-induced obese and ob/ob mice shifted FGF21 responses from WAT toward energy-combusting BAT. In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT. (Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu