| Texto completo | |
| Autor(es): |
Guedes, J. A. C.
;
Esteves, J., V
;
Morais, M. R.
;
Zorn, T. M.
;
Furuya, D. T.
Número total de Autores: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BONE; v. 115, p. 15-pg., 2018-10-01. |
| Resumo | |
Aims/hypothesis: The discovery of osteocalcin, a protein synthetized by osteoblasts, as a hormone that has positive effects on insulin resistance, contributed to support the concept of bone as an endocrine organ. However, very little is known about the molecular pathways involved in osteocalcin improved-insulin resistance. The present study aimed to investigate the mechanisms of action of osteocalcin on insulin resistance and inflammation in obese mice and 3T3-L1 adipocytes. Methods and results: Lean control, saline-treated obese and uncarboxylated osteocalcin (uOC)-treated obese mice were subjected to insulin tolerance test in vivo. Blood was collect for biochemical/metabolic profile analysis; and, skeletal muscle, white adipose tissue (WAT) and bone were collected for protein (Western blotting) and mRNA (RT-qPCR) analysis. uOC effects on insulin resistance and inflammation were also investigated in 3T3-L1 adipocytes challenged with tumor necrosis factor. Osteocalcin treatment improved in vivo insulin resistance in obese mice. In WAT, osteocalcin had positive effects such as (1) WAT weight reduction; (2) upregulation of glucose transporter (GLUT) 4 protein and its mRNA (Slc2a4); (3) improved insulin-induced AKT phosphorylation; (4) downregulation of several genes involved in inflammation and inflammassome transcriptional machinery, and (5) reduction of the density of macrophage in crown-like structures (histomorphometrical analysis). Notably, in 3T3-L1 adipocytes, osteocalcin restored Slc2a4/ GLUT4 content and reduced the expression of inflammatory genes after TNF-a challenge; moreover, osteocalcin treatment increased ART phosphorylation induced by insulin. Finally, it was observed that in bone, osteocalcin improves insulin resistance by increasing insulin-induced ART phosphorylation and reducing the expression of genes involved in bone insulin resistance, resulting in increased secretion of uncarboxylated osteocalcin in circulation. Conclusion: We provided some mechanisms of action for osteocalcin in the amelioration of insulin resistance in obesity: in WAT, osteocalcin improves insulin resistance by decreasing inflammation, and increasing insulin signaling and the expression of Slc2a4/GLUT4; and, in bone, osteocalcin increases the secretion of uncarboxylated osteocalcin by improving insulin resistance. (C) 2017 Elsevier Inc. All rights reserved. (AU) | |
| Processo FAPESP: | 14/10007-5 - Regulação do metabolismo da glicose pelo osso: ações da osteocalcina na resistência à insulina e inflamação em tecidos adiposo e hepático |
| Beneficiário: | Daniela Tomie Furuya |
| Modalidade de apoio: | Bolsas no Brasil - Jovens Pesquisadores |
| Processo FAPESP: | 13/18841-1 - Regulação do metabolismo da glicose pelo osso: ações da osteocalcina na resistência à insulina e inflamação em tecidos adiposo e hepático |
| Beneficiário: | Daniela Tomie Furuya |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 15/01576-9 - Ação da osteocalcina no acúmulo de lípides via GLUT2/SREBP-1c em hepatócitos e tecido hepático de camundongos obesos |
| Beneficiário: | José Augusto Cipriano Guedes |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |