Omentin -1 antagonizes high fat-induced bone loss in rats and promotes bone growth via AMPK/mTORC1/ PPAR-γ and GDF-11 signaling pathway

El-Malkey, Nanees Fouad; Elwany, Nisreen Elnagy; Goda, -	Nehal; Aref, Mohammed; Khalil, Sama Salah

doi:10.21608/zumj.2023.205450.2788

Omentin -1 antagonizes high fat-induced bone loss in rats and promotes bone growth via AMPK/mTORC1/ PPAR-γ and GDF-11 signaling pathway

Document Type : Original Article

Authors

¹ Department of physiology, faculty of medicine, zagazig University

² Pharmacology department, zagazig University, faculty of medicine

³ Department of Histology & Cytology Faculty of Veterinary Medicine, Zagazig University,Zagazig,Egypt

⁴ Anatomy department, faculty of Veterinary medicine, Zagazig University

⁵ Medical physiology, Zagazig University, Egypt, ElSharquia, Zagazig.

10.21608/zumj.2023.205450.2788

Abstract

Abstract

Background: Obesity induces bone related diseases as a consequence of reduced bone formation and unwarranted bone resorption. Therefore, the possible impact of adipokines on osteogenesis has been considered. Nevertheless, the osteogenic properties of omentin 1 are indistinct and contentious. The objective of the current work was to determine the regulatory effects of omentin 1 on bone turnover, along with to explore the fundamental molecular mechanisms in obese rats.

Methods: The present study investigated the effects of intraperitoneal omentin-1 injection (8 μg/kg, once daily, for 14 days) in rats after feeding a high-fat diet for 10 weeks to induce obesity. Metabolic parameters and bone dry and ash weights were measured; serum calcium, phosphorus, alkaline phosphatase, and Growth differentiation factor-11 (GDF-11), and femur histopathological changes were analyzed. Additionally, we investigated the effect of omentin-1 treatment on AMP protein-kinase (AMPK), mammalian target rapamycin (mTORC1), and nuclear receptor peroxisome proliferator-activated receptor-γ (PPAR-γ) expression.

Results: The results revealed significant improvement in metabolic, bone biochemical parameters, and histopathological changes in the omentin-1 treated group with a significant increase in area % of bone. A Significant down-regulation of mTORC1 was identified through AMPK/mTORC1/PPAR-γ pathway accompanied by an increase in serum GDF-11. Conclusion: Omentin 1 can significantly promote bone health and viability via down-regulation of the AMPK/mTORC1/PPAR-γ signaling pathway, and up-regulation of serum GDF-11, in that way it can promote bone formation and prevent osteoporosis.

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