Background: Obesity has a detrimental role in overall health. Obesity can be driven by consuming a high-fat diet (HFD), resulting in dysregulation in bone metabolism. Preptin is a novel peptide hormone derived from pro-IGF-2. Preptin is co-secreted with insulin, from pancreatic β-cells and increases glucose-stimulated insulin secretion. Preptin also has effects on osteoblasts. We tested the hypothesis that HFD negatively affects bone microarchitecture, and preptin deficiency worsens this phenotype using a preptin knockout (KO) mouse fed HFD.
Methods: Wild type (WT) and KO C57BL/6J mice were placed onto either control diet or HFD for 14 weeks at 8 weeks of age. Metabolic phenotypes were evaluated by weekly fasted blood glucose measurements at 10, 17 and 21 weeks of age. An oral glucose tolerance test was performed at 13 weeks of study (n=12-15/sex/genotype). Femurs were excised at 23 weeks of age and analysed using micro-computed tomography.
Results: Bodyweights of preptin KO mice were different in both females and males at 23 weeks of age. Male preptin KO in both CD and HFD had increased blood glucose concentration at 30- and 60- minutes post-glucose during glucose tolerance test (GTT) compared to WT mice. There were no metabolic differences in females. HFD affected both cortical and trabecular indices with no differences between genotypes. HFD decreased trabecular bone volume fraction (BV/TV) in WT and KO male mice by 40% and 29%, respectively, and in female mice by 51% and 44%, respectively. Cortical bone area was decreased in WT and KO male mice by 13% and 6%, respectively, and in female mice by 7% and 9%, respectively.
Discussion: The findings gathered from the results indicate that deletion of preptin did not elicit an overall deleterious effect on trabecular and cortical bone. The introduction of HFD contributed to weight gain, and metabolic disturbance resulting in glucose intolerance and compromises bone health in the trabecular and cortical bones in both sexes. Despite the removal of the gene encoding preptin, the effects of HFD on bone microarchitecture had no other further detrimental effects on bone health.