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Effect of energy balance on bone mass and marrow fat in type 1 diabetes mellitus

Grant number: 14/14505-0
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): January 12, 2015
Effective date (End): November 11, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Francisco José Albuquerque de Paula
Grantee:Adriana Lelis Carvalho
Supervisor abroad: Clifford J. Rosen
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Maine Medical Center, Scarborough, United States  
Associated to the scholarship:13/09853-6 - Relationship between visceral, hepatic and bone adiposity with bone mineral density and fracture occurrence in type 1 diabetes mellitus, BP.DR


A great interest has emerged in the investigation about the metabolic network involving bone and adipose tissue on both diabetes mellitus (DM) and osteoporosis. Visceral adipose tissue is not only involved on the generation of insulin resistance, but also seem to exert a negative influence on the skeleton mediated by inflammatory cytokines and adipokines. In this context, adiponectin an adipocyte marker of insulin sensitivity has been evaluated regarding its potential effect on bone remodeling. On the other hand, another aspect to be taken into consideration is the role of bone marrow fat on bone loss, which needs more clarification especially in DM. In the present proposal, we intend to evaluate bone loss and marrow adiposity in T1DM mice previously submitted to caloric restriction. Additionally, the adiponectin (APN) levels will be followed during the calorie restriction and diabetes induction periods. The effects of APN in the differentiation of bone marrow mesenchymal stem cell (BMMSC) will also be investigated in vitro. Mice will be submitted to a 4 weeks caloric restriction period, during this interval the animals will be subjected to streptozotocin injection for induction of T1DM, on day 16. The groups will be followed for an additional 4 weeks-period. Bone BMD and body composition will be measured by DXA, body composition and bone marrow fat will be assessed by Nuclear Magnetic Resonance. Blood sample will be drawn to measure bone remodeling markers and APN. Micro-computed tomography (µCT) and histomorphometry analysis will be performed. Tibias and femur will also be collected to assess the influence of APN on BMMSC differentiation. (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)
CARVALHO, ADRIANA L.; MASSARO, BIANCA; E SILVA, LUCIANA T. P.; SALMON, CARLOS E. G.; FUKADA, SANDRA Y.; NOGUEIRA-BARBOSA, MARCELLO H.; ELIAS, JR., JORGE; FREITAS, MARIA C. F.; COURI, CARLOS E. B.; OLIVEIRA, MARIA C.; SIMOES, BELINDA P.; ROSEN, CLIFFORD J.; DE PAULA, FRANCISCO J. A. Emerging Aspects of the Body Composition, Bone Marrow Adipose Tissue and Skeletal Phenotypes in Type 1 Diabetes Mellitus. JOURNAL OF CLINICAL DENSITOMETRY, v. 22, n. 3, p. 420-428, JUL-SEP 2019. Web of Science Citations: 2.
CARVALHO, ADRIANA LELIS; DEMAMBRO, VICTORIA E.; GUNTUR, ANYONYA R.; LE, PHUONG; NAGANO, KENICHI; BARON, ROLAND; ALBUQUERQUE DE PAULA, FRANCISCO JOSE; MOTYL, KATHERINE J. High fat diet attenuates hyperglycemia, body composition changes, and bone loss in male streptozotocin-induced type 1 diabetic mice. Journal of Cellular Physiology, v. 233, n. 2, p. 1585-1600, FEB 2018. Web of Science Citations: 3.
MOTYL, KATHERINE J.; GUNTUR, ANYONYA R.; CARVALHO, ADRIANA LELIS; ROSEN, CLIFFORD J. Energy Metabolism of Bone. TOXICOLOGIC PATHOLOGY, v. 45, n. 7, p. 887-893, OCT 2017. Web of Science Citations: 4.

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