Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats

Abstract

The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, nZ12) or a sham operation (S, nZ12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats.

Association of Insulin Resistance and β-cell Function With Bone Turnover Biomarkers in Dysglycemia Patients

“…Thus, there could exist an inner link for bone biomarkers to estimate the relationship between the process of osteoporosis and the function of pancreatic or insulin resistance. Previous research held the opinion that insulin resistance had a negative relationship with bone formation and a positive interrelation with bone resorption and that pancreatic function had the opposite relationship (35,36). However, our results from this study showed that when IR was aggravated or b-cell function decreased, the metabolic disorders of bone agitated not only formation but also resorption.…”

Metabolic milieu associates with impaired skeletal characteristics in obesity

“…In rodent models, obesity accompanied with insulin resistance is demonstrated to decrease osteoblastic proliferation, increase osteoblastic apoptosis, enhance osteoblastic insulin resistance and increase bone porosity [30] which are marked as impaired bone quality especially in trabecular bone sites. In the present study, inverse associations of HOMA with P1NP, CTX, TRAC5b and multiple bone characteristics were observed almost exclusively in males.…”

Complex interplay among adiposity, insulin resistance and bone health

“…Mice lacking osteoblast insulin receptor exhibit impaired postnatal bone formation . High‐fat fed rats exhibit osteoblastic insulin resistance, resulting in shorter osteoblastic survival .…”