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Food restriction and refeeding: short and medium term effects on growth cartilage and tibial bone quality of growing rats

Grant number: 20/00529-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2020
Effective date (End): November 30, 2022
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:José Batista Volpon
Grantee:Patrícia Madalena San Gregório Guedes
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Malnutrition occurs due to general or specific depletion of essential nutrients and has a high prevalence worldwide. It affects several organs, with greater impact in children, in which the impairments may persist for their entire life, even if normal nutrition is restored. Although the effects of malnutrition on the individual development is quite evident, little is known about its repercussions on the skeletal system, such as growth and bone quality. The purpose of this research is to evaluate the impact of food restriction and subsequent feedback on the growth cartilage and bone tissue in rats during different developmental periods. Materials and methods: 100 male Wistar Hannover rats will be used in this study, with initial body mass of 70 grams, divided into three experimental groups: (1) CON: control rats, followed for 12 weeks; (2) FR: rats subjected to food restriction for 12 weeks and; (2) FRF: rats subjected to food restriction and subsequent feedback. In the first group, the corresponding control (CON) will receive normal diet and the comparison will be between them after twelve weeks (FR12w and CON12w). The third group will be subdivided into three subgroups after six weeks of dietary restriction and will be accompanied by two (FRF2w), four (FRF4w), and six weeks (FRF6w), in whose periods they will be fed back (n=20/subgroup). Malnutrition will be obtained by offering 50% of the food intake at the control rats on the previous day. The methods of evaluation of trabecular and cortical bones and growth cartilage will be performed by histology, densitomety (DXA), micro-computed tomography (qualitative and quantitative evaluation of bone microarchitecture), histomorphometry (quantification of bone and collagen deposition), immunohistochemistry (for bone formation and resorption assessment: OPG, RANK and RANKL), gene expression (RUNX-2, RANKL, OPG and TGF²-1) and mechanical analysis. Also, serum analysis of bone formation and resorption markers will be performed (OPG, RANK, RANKL, PINP, CTX-I, IGF-1). The results will characterize the effects of dietary restriction and feedback on growth cartilage and bone tissue in growing rats. (AU)