Neonatal overfeeding impairs differentiation potential of mice subcutaneous adipose mesenchymal stem cells

Abstract

Nutritional changes in the development (intrauterine life and postnatal period) may trigger long-term pathophysiological complications such as obesity and cardiovascular disease. Metabolic programming leads to organs and tissues modifications, including adipose tissue, with increased lipogenesis, production of inflammatory cytokines, and decreased glucose uptake. However, stem cells participation in adipose tissue dysfunctions triggered by overfeeding during lactation has not been elucidated. Therefore, this study was the first to evaluate the effect of metabolic programming on adipose mesenchymal stem cells (ASC) from mice submitted to overfeeding during lactation, using the litter reduction model. Cells were evaluated for proliferation capacity, viability, immunophenotyping, and reactive oxygen species (ROS) production. The content of UCP-2 and PGC1-α was determined by Western Blot. ASC differentiation potential in adipogenic and osteogenic environments was also evaluated, as well the markers of adipogenic differentiation (PPAR-γ and FAB4) and osteogenic differentiation (osteocalcin) by RT-qPCR. Results indicated that neonatal overfeeding does not affect ASC proliferation, ROS production, and viability. However, differentiation potential and proteins related to metabolism were altered. ASC from overfed group presented increased adipogenic differentiation, decreased osteogenic differentiation, and also showed increased PGC1-α protein content and reduced UCP-2 expression. Thus, ASC may be involved with the increased adiposity observed in neonatal overfeeding, and its therapeutic potential may be affected.

Neonatal Resveratrol and Nicotinamide Riboside Supplementations Sex-Dependently Affect Beige Transcriptional Programming of Preadipocytes in Mouse Adipose Tissue

“…Another novel aspect of the present work is the use of the primary culture model, which so far has been little exploited in the field of nutritional programming, despite its potential relevance for this field. To our knowledge, only one recent report has used a similar approach, to demonstrate that neonatal overfeeding affects the differentiation capacities of adipose tissue mesenchymal stem cells (Dias et al, 2018).…”

Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction

“…49 In contrast, our previous data demonstrate enhanced adipogenesis and osteogenesis, but impaired chondrogenic differentiation in murine ASCs from high-fat diet-induced C57BL6/J obese mice. 17 Overfeeding of neonatal mice before weaning induces metabolic re-programming of ASCs toward increased adipogenic differentiation, and decreased osteogenic differentiation, 50 demonstrating that dysregulation in obesity can begin early in life, which implicates a role for epigenetic regulation. DNA methylation at the 5′ site of cytosine is a critical component of the heritable and modifiable epigenetic landscape.…”

Aging and Obesity Prime the Methylome and Transcriptome of Adipose Stem Cells for Disease and Dysfunction

“…49 In contrast, our previous data demonstrate enhanced adipogenesis and osteogenesis, but impaired chondrogenic differentiation in murine ASCs from high-fat diet-induced C57BL6/J obese mice. 17 Overfeeding of neonatal mice before weaning induces metabolic re-programming of ASCs towards increased adipogenic differentiation, and decreased osteogenic differentiation, 50 demonstrating that dysregulation in obesity can begin early in life, which implicates a role for epigenetic regulation. DNA methylation at the 5' site of cytosine is a critical component of the heritable and modifiable epigenetic landscape.…”