Effect of Obestatin on Bone Turnover in Normal and Obese Male Albino Rats

Abstract
Background: Obestatin is a peptide hormone derived from the posttranslational cleavage of the same peptide precursor as ghrelin, it has been shown to regulate food intake, pancreatic, adipocyte, cardiac function as well as cell proliferation, however, to date, no studies have shown the effect of obestatin on bone turnover.
Aim of Study: This work was designed to investigate the effects of obestatin on bone metabolism in normal and obese rats and to explain the possible underlying mechanisms.
Material and Methods: Experiments conducted on 32 healthy adult male albino rats, which were randomly and equally divided into 2 groups, group I (normal) and group II [high fat diet induced obese group (HFD)]. Each group further subdivided into equal 2 subgroups: Group a (received a single intraperotoneal (ip) injection of 100ml saline daily for 30 consecutive days) and group b (daily ip injected with obestatin "1nmol/100gm BW" for 30 consecutive days). In all groups, gene expression of osteocalcin (OC), osteoprotegerin (OPG) and Receptor activator nuclear factor kB ligand (RANKL) bone markers were measured by real time PCR (RT-PCR), serum calcitonin, interleukin-6 (IL-6), insulin, glucose, total cholesterol (TC), total triglycride (TG) were measured, HO-MA-IR and BMI were calculated, bone histopathology was also done.
Results: In both normal and obese groups, obestatin caused significant decrease in RANKL, significant increase in oste-opetrogenin, OPG/RANKL ratio, osteocalcin expression and serum calcitonin in comparison to their control, in subgroup Ib (obestatin treated normal group), there was significant decrease in BMI, however, there was non-significant change in serum glucose, insulin levels, HOMA-IR index, TC, TG, IL 6 levels in comparison to subgroup Ia. While, in subgroup IIb (obestatin treated obese group), there was a significant decrease in BMI, serum glucose, TG, TC, serum insulin levels, HOMA-IR index and IL 6 levels in comparison to subgroup IIa. In bone histopathology, subgroup Ib showing slight increase in bone trabeculae thickness in comparison to the control and subgroup IIa showed thin atrophic bone trabeculae with wide marrow spaces. While, subgroup IIb showed in-creased bone trabeculae thickness in comparison to the later.
Conclusion: Obestatin has anabolic effect on bone in normal and obese rats, which it can be used in regime diet induced weight loss, as it prevent the decrease of bone mass that accompany weight loss.