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Regulation of glucose metabolism by the bone: role of osteocalcin in insulin resistance and inflammation of adipose tissue and liver


Recent studies have shown that the uncarboxylated form of osteocalcin (uOCN), an osteoblat-derived protein, acts as a hormone that has a positive effect on insulin secretion and sensitivity, as well as on fat metabolism. These observations led to the fascinating discovery of bone as an endocrine gland. However, little is known about the molecular mechanism of uOCN actions on glucose metabolism. Considering that obese subjects has reduced circulating levels of uOCN, and that obesity is a state of insulin resistance and inflammation, the aim of the present project is to unravel the molecular mechanisms of uOCN action on insulin resistance and inflammation in adipose tissue and liver. For this, the role of OCN putative receptor, GPRC6A, will be investigated through gene silencing (RNA interference technology). Besides, the present study will address the possibility of OCN/uOCN secretion by adipocytes and the mechanisms involved in the OCN post-translational modifications in osteoblasts and bone of obese mice. The investigation of the role of bone system in the context of endocrinology provides a project that will establish a new line of research in the institute in which it will be conducted. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GUEDES, J. A. C.; ESTEVES, V, J.; MORAIS, M. R.; ZORN, T. M.; FURUYA, D. T. Osteocalcin improves insulin resistance and inflammation in obese mice: Participation of white adipose tissue and bone. BONE, v. 115, n. SI, p. 68-82, OCT 2018. Web of Science Citations: 8.
EBERSBACH-SILVA, PATRICIA; POLETTO, ANA CLAUDIA; DAVID-SILVA, ALINE; SERAPHIM, PATRICIA MONTEIRO; ANHE, GABRIEL FORATO; PASSARELLI, MARISA; FURUYA, DANIELA TOMIE; MACHADO, UBIRATAN FABRES. Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement. LIPIDS IN HEALTH AND DISEASE, v. 17, APR 2 2018. Web of Science Citations: 0.
POLETTO, ANA CLAUDIA; DAVID-SILVA, ALINE; DE MELO YAMAMOTO, ALINE PEDRO; MACHADO, UBIRATAN FABRES; FURUYA, DANIELA TOMIE. Reduced Slc2a4/GLUT4 expression in subcutaneous adipose tissue of monosodium glutamate obese mice is recovered after atorvastatin treatment. DIABETOLOGY & METABOLIC SYNDROME, v. 7, MAR 14 2015. Web of Science Citations: 12.

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