MicroRNA-29a in Osteoblasts Represses High-Fat Diet-Mediated Osteoporosis and Body Adiposis through Targeting Leptin

International Journal of Molecular Sciences

Wei-Shiung Lian¹  Yu-Shan Chen¹  Feng-Sheng Wang¹  Shao-Yu Wang¹  Holger Jahr²  Re-Wen Wu³  Jih-Yang Ko³ 

[1] Core Laboratory for Phenomics and Diagnostic, Department of Medical Research, Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, 52074 Aachen, Germany;Department of Orthopedic Surgery, Chang Gung University College of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan;

关键词: microRNA-29a;    bone loss;    visceral fat deposit;    heat production;    leptin;   

DOI  :  10.3390/ijms22179135

来源: DOAJ

【 摘 要 】

Skeletal tissue involves systemic adipose tissue metabolism and energy expenditure. MicroRNA signaling controls high-fat diet (HFD)-induced bone and fat homeostasis dysregulation remains uncertain. This study revealed that transgenic overexpression of miR-29a under control of osteocalcin promoter in osteoblasts (miR-29aTg) attenuated HFD-mediated body overweight, hyperglycemia, and hypercholesterolemia. HFD-fed miR-29aTg mice showed less bone mass loss, fatty marrow, and visceral fat mass together with increased subscapular brown fat mass than HFD-fed wild-type mice. HFD-induced O₂ underconsumption, respiratory quotient repression, and heat underproduction were attenuated in miR-29aTg mice. In vitro, miR-29a overexpression repressed transcriptomic landscapes of the adipocytokine signaling pathway, fatty acid metabolism, and lipid transport, etc., of bone marrow mesenchymal progenitor cells. Forced miR-29a expression promoted osteogenic differentiation but inhibited adipocyte formation. miR-29a signaling promoted brown/beige adipocyte markers Ucp-1, Pgc-1α, P2rx5, and Pat2 expression and inhibited white adipocyte markers Tcf21 and Hoxc9 expression. The microRNA also reduced peroxisome formation and leptin expression during adipocyte formation and downregulated HFD-induced leptin expression in bone tissue. Taken together, miR-29a controlled leptin signaling and brown/beige adipocyte formation of osteogenic progenitor cells to preserve bone anabolism, which reversed HFD-induced energy underutilization and visceral fat overproduction. This study sheds light on a new molecular mechanism by which bone integrity counteracts HFD-induced whole-body fat overproduction.

【 授权许可】

Unknown