title: FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues.
abstract: 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.
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Christian
authors: C
authors: Schlein
authors: Cardiovascular Metabolic and Endocrine Diseases (CVMED), Pfizer, 610 Main Street, Cambridge, MA 02139, USA.
authors: Saswata
authors: S
authors: Talukdar
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Markus
authors: M
authors: Heine
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Alexander W
authors: AW
authors: Fischer
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Lucia M
authors: LM
authors: Krott
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Stefan K
authors: SK
authors: Nilsson
authors: Cardiovascular Metabolic and Endocrine Diseases (CVMED), Pfizer, 610 Main Street, Cambridge, MA 02139, USA.
authors: Martin B
authors: MB
authors: Brenner
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors: Joerg
authors: J
authors: Heeren
authors: Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: l.scheja@uke.de.
authors: Ludger
authors: L
authors: Scheja
mesh_terms: D052438:Adipocytes, White / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology* / Q000627:therapeutic use; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014280:Triglycerides / Q000097:blood*
chemical_list: D000960:Hypolipidemic Agents; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors