The role of HDL metabolic pathways in the development of brown-like phenotype in bone marrow of mice

• Κύριος συγγραφέας: Καστρενοπούλου, Αφροδίτη Γρηγορία
• Άλλοι συγγραφείς: Kastrenopoulou, Afroditi Grigoria
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: HDL; Brown adipose tissue (BAT); UCP1; ApoA1; ApoAI; Lipoproteins; Φαιός λιπώδης; Λιποπρωτεΐνες

Brown adipose tissue (BAT) has anabolic effect on osteoblasts. We have recently documented that deficiency of apolipoprotein A1 (ApoA1), key-element of HDL biogenesis, results in decreased osteoblastic function in mice. In the present study we investigated whether ApoA1 deficiency (thus impaired HDL), induces a BAT-like phenotype in mice bone marrow. In our research, we used 12-week-old male ApoA1 deficient (ApoA1-/-) and wild-type mice (5 mice/group). Whole bone marrow cells (WBMCs) were isolated from mice femora. Histological/histomorphometrical analysis for bone marrow adipocytes was applied on mice femora. The expression levels of the master regulators of white adipose tissue (WAT), PPARγ and CEBPa, the adipokines leptin and adiponectin secreted from WAT, and the BAT-like genes UCP1 (uncoupling protein-1), PGC1a (a transcriptional coactivator of UCP1), PAT2 (proton assistant amino acid transporter-2 and deiodinase iodothyronine Type-II (Dio2)] were assessed using qRT-PCR. Additionally, we evaluated the mRNA levels of VEGF (vascular endothelial growth factor), that has been found to be related to adipocytes with brown-like phenotype. Histological/histomorphometric analysis revealed that ApoA1-/- mice had significantly elevated adipocyte area (n=5, p=0.005) in comparison to the WT. Accordingly, mRNA expression of PPARγ (p=0.04), CEBPa (p=0.0026) and adiponectin (p=0.012), was significantly increased in the ApoA1-/- mice compared to WT. On the contrary, the BAT-like markers UCP1 (p=0.052), PGCA1 (p=0.0033), PAT2 (p=0.0052) and Dio2 (p=0.011), were greatly reduced in the ApoA1-/- mice. The mRNA of Leptin (p=0.0001) and VEGF (p=0.0029) also displayed remarkable reduction in the ApoA1 knock-out animals. ApoA1 deficiency is associated with elevated WAT and WAT-related genes in mice BM. Moreover, Apo1 knock-out mice display reduced expression of BAT-like genes through mechanisms that warrant further investigation. Since BAT has anabolic effects on skeleton, our data further support our previous findings that shortage of ApoA1 (and hence HDL), is associated with reduced osteoblastic activity and decreased bone mass. Therefore, we highlight the interesting possibility that application of BAT-inducing therapies might offer additional therapeutic solutions against bone-related pathologies, including metabolic and neoplastic diseases.