Caracterização das células-tronco mesenquimais obtidas do tecido adiposo de camundongos Swiss submetidos à hiperalimentação na lactação

• Autor(a) principal: Dias, Isabelle dos Santos Xavier
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12788
• topic: Stem Cells; Obesity; Metabolic programming; Hyperphagia; Células-Tronco; Obesidade; Programação metabólica; Hiperfagia; Células- tronco; Obesidade; Lactação; CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA

Obesity is characterized as an increase in adipose tissue and may be associated with genetic, environmental and poor eating habits. Developmental nutritional changes (intrauterine life and postnatal period) may trigger long-term pathophysiological complications such as insulin resistance, obesity and increased cardiovascular risk in a process called metabolic programming. Metabolic programming triggers systemic alterations, besides affecting functions of several cell types such as mitochondrial dysfunction, decreased viability and proliferation. Therefore, the objective of this work was to analyze the effects of metabolic programming on adipose tissue mesenchymal stem cells (ASC) of animals that were submitted to post natal overfeeding (PNOF) using the litter reduction model. These cells were evaluated for cell proliferation, viability, immunophenotyping and production of reactive oxygen species. The content of UCP-2 and PGC1-α was determined by Western blotting. The potential of differentiation of ASC in adipogenic and osteogenic environments was evaluated, as well as the analysis of markers of adipogenic differentiation (PPAR-γ and FAB4) and osteogenic differentiation (Osteocalcin) by PCR. The results showed that there was no change in proliferation and viability of cells compared to normal cells, but the ASC of the PNOF group had a lower percentage of CD105 + CD45- cells. The ASC of both groups did not present significant difference regarding cell viability and reactive oxygen species (ROS). The content of UCP-2 was lower in the ASC of PNOF animals, while the content of PGC1-α increased in these cells. An increase in the adipogenic potential in the ASC of the PNOF group was observed by the quantification by Oil Red. When analyzing the PPAR-γ marker in the ASC of the hyperlacted group there was an increase in the gene expression. The potential for osteogenic differentiation showed a decrease in differentiated ASC from the PNOF group in quantification by alizarin red. The analysis of the differentiation marker Osteocalcin showed a decrease in the gene expression in the ASC of the PNOF group. The lower percentage of CD105 + cells in the ASC of the PNOF group may be related to a lower potential for osteogenic differentiation, since this receptor participates in the activation of the osteogenic differentiation pathway through TGF-β modulation. UCP-2 protein is known to increase basal metabolic rate, prevent ROS production and transport of fatty acids. The decrease of this protein in the ASC of the PNOF group may be related to a decrease in the respiration rate of these cells and with lipotoxicity of the mitochondria. The increase of PGC1-α observed in PNOF ASC suggests a greater impairment of these cells with adipogenic differentiation. Thus, this study showed that hyperalimentation in the postnatal period is capable of altering the mitochondrial metabolism and potential differentiation of ASC, but without impairing viability, proliferation and ROS production.