Dietary Protein Restriction and FGF21 Influence Bone Morphology

Abstract

Dietary modifications, including protein restriction, affect multiple organs. Previous work shows that protein restriction induces adaptive changes in food intake, growth, and metabolism, and that these effects are lost in FGF21 deficient mice. This indicates FGF21 is required for this response. While previous work has shown FGF21 affects growth plate cartilage, no work has yet been done to identify the impact of these combined conditions on bone growth and remodeling, despite changes in overall size and weight in previous studies. The purpose of the current study was to identify whether dietary protein restriction in wild‐type (WT) or FGF21‐deficient (KO) mice impacts bone. WT or KO mice were placed on a control (NP, 20% casein) or low‐protein (LP, 5% casein) diet (n=39, 9‐10/group) starting at 17.5 weeks of age for 27 weeks. Following sacrifice, cortical and trabecular bone morphology within the femur was evaluated with micro‐CT. No significant differences were identified in bone length, however significant differences were found in trabecular bone volume/total volume (BV/TV; p<0.001). Overall, LP groups had significantly lower values than the NP groups within the same genotype, and KO mice had significantly lower BV/TV values than WT. Cortical area was significantly decreased in the WT‐LP diet compared to WT‐NP (p<0.001), but it was not different in KO mice. However, cortical marrow space area was significantly decreased in KO mice when compared to WTs (p<0.01). These data demonstrate that prolonged dietary protein restriction exerts a marked negative effect on bone health, and that loss of FGF21 signaling alters but doesn't block this negative effect.