title: FGF21 Is Not a Major Mediator for Bone Homeostasis or Metabolic Actions of PPARα and PPARγ Agonists.
abstract: Results of prior studies suggest that fibroblast growth factor 21 (FGF21) may be involved in bone turnover and in the actions of peroxisome proliferator-activated receptor (PPAR) α and γ in mice. We have conducted independent studies to examine the effects of FGF21 on bone homeostasis and the role of FGF21 in PPARα and γ actions. High-fat-diet-induced obesity (DIO) mice were administered vehicle or recombinant human FGF21 (rhFGF21) intraperitoneally at 0 (vehicle), 0.1, 1, and 3 mg/kg daily for 2 weeks. Additional groups of DIO mice received water or 10 mg/kg rosiglitazone daily. Mice treated with rhFGF21 or rosiglitazone showed expected metabolic improvements in glucose, insulin, and lipid levels. However, bone loss was not detected in rhFGF21-treated mice by dual-energy X-ray absorptiometry (DXA), micro-CT, and histomorphometric analyses. Mineral apposition rate, a key bone formation parameter, was unchanged by rhFGF21, while significantly decreased by rosiglitazone in DIO mice. Bone resorption markers, OPG/RANKL mRNA expression, and histological bone resorption indices were unchanged by rhFGF21 or rosiglitazone. Bone marrow fat was unchanged by rhFGF21, while increased by rosiglitazone. Furthermore, FGF21 knockout mice did not show high bone mass phenotype. Treatment with PPARα or PPARγ agonists caused similar metabolic effects in FGF21 knockout and wild-type mice. These results contrast with previous findings and suggest that FGF21 is not critical for bone homeostasis or actions of PPARα and PPARγ. © 2016 American Society for Bone and Mineral Research.
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Xiaodong
authors: X
authors: Li
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Shanaka
authors: S
authors: Stanislaus
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Frank
authors: F
authors: Asuncion
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Qing-Tian
authors: QT
authors: Niu
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Narumol
authors: N
authors: Chinookoswong
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Kelly
authors: K
authors: Villasenor
authors: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA, USA.
authors: Jin
authors: J
authors: Wang
authors: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA, USA.
authors: Philip
authors: P
authors: Wong
authors: Department of Comparative Biology and Safety Sciences, Amgen Inc., Thousand Oaks, CA, USA.
authors: Rogely
authors: R
authors: Boyce
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Denise
authors: D
authors: Dwyer
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Chun-Ya
authors: CY
authors: Han
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Michelle M
authors: MM
authors: Chen
authors: Department of Inflammation, Amgen Inc., Thousand Oaks, CA, USA.
authors: Benxian
authors: B
authors: Liu
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Marina
authors: M
authors: Stolina
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Hua Zhu
authors: HZ
authors: Ke
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Michael S
authors: MS
authors: Ominsky
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Murielle M
authors: MM
authors: Véniant
authors: Department of Cardiometabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
authors: Jing
authors: J
authors: Xu
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000235:genetics; D047493:PPAR alpha / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D004041:Dietary Fats; D007328:Insulin; D053244:Osteoprotegerin; D047493:PPAR alpha; D047495:PPAR gamma; D053245:RANK Ligand; D045162:Thiazolidinediones; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; C414620:fibroblast growth factor 21; D000077154:Rosiglitazone; D005346:Fibroblast Growth Factors; D005947:Glucose
keywords: BONE MASS; FGF21; PPARα; PPARγ