title: Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice.
abstract: Bone marrow cells (BMCs) are the main type of cells used for transplantation therapies. Obesity, a major world health problem, has been demonstrated to affect various tissues, including bone marrow. This could compromise the success of such therapies. One of the main mechanisms underlying the pathogenesis of obesity is mitochondrial dysfunction, and recent data have suggested an important role for mitochondrial metabolism in the regulation of stem cell proliferation and differentiation. Since the potential use of BMCs for clinical therapies depends on their viability and capacity to proliferate and/or differentiate properly, the analysis of mitochondrial function and cell viability could be important approaches for evaluating BMC quality in the context of obesity. We therefore compared BMCs from a control group (CG) and an obese group (OG) of mice and evaluated their mitochondrial function, proliferation capacity, apoptosis, and levels of proteins involved in energy metabolism. BMCs from OG had increased apoptosis and decreased proliferation rates compared with CG. Mitochondrial respiratory capacity, biogenesis, and the coupling between oxidative phosphorylation and ATP synthesis were significantly decreased in OG compared with CG, in correlation with increased levels of uncoupling protein 2 and reduced peroxisome proliferator-activated receptor-coactivator 1α content. OG also had decreased amounts of the glucose transporter GLUT-1 and insulin receptor (IRβ). Thus, Western-diet-induced obesity leads to mitochondrial dysfunction and reduced proliferative capacity in BMCs, changes that, in turn, might compromise the success of therapies utilizing these cells.
authors.affiliation: Laboratory of Cell Culture, Department of Histology and Embryology, Institute of Biology, State University of Rio de Janeiro, Av. Professor Manoel de Abreu 444, Rio de Janeiro, Brazil.
authors.forename: Genilza Pereira
authors.initials: GP
authors.lastname: de Oliveira
authors.forename: Erika
authors.initials: E
authors.lastname: Cortez
authors.forename: Graça Justo
authors.initials: GJ
authors.lastname: Araujo
authors.forename: Katia Costa
authors.initials: KC
authors.lastname: de Carvalho Sabino
authors.forename: Fabiana Alves
authors.initials: FA
authors.lastname: Neves
authors.forename: Amélia Faustino
authors.initials: AF
authors.lastname: Bernardo
authors.forename: Simone Nunes
authors.initials: SN
authors.lastname: de Carvalho
authors.forename: Anibal Sanchez
authors.initials: AS
authors.lastname: Moura
authors.forename: Laís
authors.initials: L
authors.lastname: Carvalho
authors.forename: Alessandra Alves
authors.initials: AA
authors.lastname: Thole
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008928:Mitochondria / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D010085:Oxidative Phosphorylation; D015398:Signal Transduction