Premium
FGF21 Is Not a Major Mediator for Bone Homeostasis or Metabolic Actions of PPARα and PPARγ Agonists
Author(s) -
Li Xiaodong,
Stanislaus Shanaka,
Asuncion Frank,
Niu QingTian,
Chinookoswong Narumol,
Villasenor Kelly,
Wang Jin,
Wong Philip,
Boyce Rogely,
Dwyer Denise,
Han ChunYa,
Chen Michelle M,
Liu Benxian,
Stolina Marina,
Ke Hua Zhu,
Ominsky Michael S,
Véniant Murielle M,
Xu Jing
Publication year - 2017
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2936
Subject(s) - rosiglitazone , endocrinology , medicine , fgf21 , osteoprotegerin , bone resorption , peroxisome proliferator activated receptor , glucose homeostasis , bone remodeling , bone mineral , chemistry , receptor , osteoporosis , diabetes mellitus , insulin resistance , fibroblast growth factor , activator (genetics)
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.