Evidence of the role of leptin in the regulation of bone formation in chronic hemodialysis

• Grant number: 11/00259-9
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2011 - June 30, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jacqueline do S Costa Teixeira Caramori
• Grantee: Jacqueline do S Costa Teixeira Caramori
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Janaina da Silva Martins ; Rosa Maria Affonso Moysés

Abstract

Rationale: The bone tissue is highly metabolic and increasingly recognized as a key player in pathways of energy control. The obesity-related hormone leptin acts on bone by inhibiting osteoclastogenesis, increased bone mass and induce transcription and secretion of fibroblast growth factor (FGF23). The actions of leptin on bone are mediated by specific receptor OBRb. In chronic kidney disease is very high leptin concentration, and evidence on their role in osteoarthritis are conflicting. So far, the relationship between serum leptin and its receptor in bone specific patients with renal osteodystrophy has not been studied.Hypothesis: Elevated serum leptin would be unable to increase bone mass and possibly in decreased receptor expression in osteoblasts OBRb of chronic kidney disease. Serum leptin should be combined with high levels of FGF23, and with insulin resistance and obesity.Objectives: To quantify receptor expression OBRb in bone tissue correlated with serum leptin and free association to evaluate the relationship of serum leptin / OBRb in rates of bone formation and resorption, as well as investigating the influence on serum levels of FGF23 in hemodialysis patients chronic. Research plan: Cross-sectional study on 60 patients with renal osteodystrophy, Hospital das Clinicas, Universidade Estadual Paulista. Will be included from January 2011 to January 2012 patients who agree with the bone biopsy and sign informed consent. Shall be excluded patients younger than 18 years or less than three months of hemodialysis, who have received steroids and / or immunomodulatory drugs in the past six months, severe liver disease or cancer. Is anthropometric measurements, biochemical analysis for determination of free leptin, intact PTH and FGF23, after fasting for 12 hours. Will be held on bone histomorphometry and quantification of the expression of OBRb reaction by quantitative polymerase chain in real time (RT-qPCR). Expected results: Rolling back the participation of leptin in renal osteodystrophy, quantifying and describing the expression of OBRb, and investigating its involvement in serumFGF23. Conclusion: It is expected to strengthen the experimental evidence of the effect of leptin on the pathophysiology of bone metabolism, linking this research to the findings of energy metabolism. (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)

MARTINS, JANAINA DA SILVA; CASTRO, JOAO HENRIQUE; RUEDA, NESTOR A. SAINZ; DOS REIS, LUCIENE MACHADO; JORGETTI, VANDA; AFFONSO MOYSES, ROSA MARIA; CARAMORI, JACQUELINE TEIXEIRA. Renal osteodystrophy in the obesity era: Is metabolic syndrome relevant?. PLoS One, v. 12, n. 7, JUL 18 2017. (11/00259-9)