[Mechanism of naringin in ameliorating lipid-bone metabolism disorders in postmenopausal osteoporotic rats via activation of FXR/FGF19 pathway].

This study aims to investigate the effect and mechanism of naringin on anti-osteoporosis by regulating lipid-bone balance. Thirty healthy female SD rats(8-week-old, SPF grade) were selected and randomly divided into a sham group, an ovariectomy group, and a naringin group. Except for the sham group, postmenopausal osteoporosis models were established for both the ovariectomy group and the naringin group by removing bilateral ovaries. Rats in the naringin group were given a naringin suspension at a dose of 100 mg·kg~(-1), while those in sham and ovariectomy groups were administered an equivalent volume of saline. Following the treatment once daily for 12 weeks, an enzyme-linked immunosorbent assay(ELISA) was used to detect the changes in the content of serum estradiol(E_2) and bone metabolism biomarkers, including procollagen type Ⅰ N-terminal propeptide(PINP), osteocalcin(OC), and tartrate-resistant acid phosphatase 5(TRACP5). Micro-CT analysis was performed to assess structural alterations in the femoral trabeculae of rats and analyze morphometric parameters of the bone. Hematoxylin-eosin(HE) and Masson staining were used to observe the histopathological changes in the bone tissue. Western blot was employed to analyze the protein expression level of osteogenesis-and adipogenesis-related factors, including peroxisome proliferator-activated receptor gamma(PPARγ), lipoprotein lipase(LPL), RUNT-related transcription factor 2(RUNX2), osterix(OSX), farnesoid X receptor(FXR), and fibroblast growth factor 19(FGF19). Additionally, immunohistochemistry was employed to evaluate the expression of key metabolic pathway proteins FXR and FGF19. After 12-week treatment, compared with the sham group, the ovariectomy group exhibited a significantly reduced level of serum E_2, PINP, and OC, alongside significantly elevated TRACP5. Compared with the ovariectomy group, the levels of serum E_2, PINP, and OC in the naringin group were significantly increased, while the level of TRACP5 was significantly decreased. Compared with the sham group, the ovariectomy group exhibited a decrease in trabecular number and continuity, sparse and disorganized arrangements, and partial formation of voids. The group also showed decreased bone mineral density(BMD), bone volume fraction(BV/TV), trabecular number(Tb.N), and trabecular thickness(Tb.Th), coupled with increased trabecular separation(Tb.Sp). Compared with the ovariectomy group, naringin intervention resulted in improved bone microarchitecture, characterized by increased trabecular number and continuity, more compact arrangements, and a significant reduction in voids. Quantitatively, this was reflected in elevated levels of BMD, BV/TV, Tb.N, and Tb.Th, alongside a significant decrease in Tb.Sp. Under light microscopy, fragmented trabeculae, uneven collagen staining, disorganized arrangements, and an expanded number and size of marrow adipocyte vacuoles were observed in the ovariectomy group, whereas naringin administration attenuated these pathological alterations. Compared with the sham group, the ovariectomy group showed a significant increase in the expression of adipogenic proteins PPARγ and LPL, alongside significant decreases in the expression of osteogenic proteins(RUNX2 and OSX) and of FXR and FGF19 proteins. In contrast, the naringin group exhibited a reversal of these trends compared to the ovariectomy group, with decreased PPARγ and LPL expression and increased RUNX2, OSX, FXR, and FGF19 expression. These findings demonstrate that naringin modulates lipid-bone metabolism homeostasis in postmenopausal osteoporotic rats, ameliorating trabecular microstructure and attenuating bone marrow adipogenesis, with its therapeutic effects mechanistically linked to the FXR/FGF19 signaling pathway.