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Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice

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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.

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References

  • Amin AH, Abd Elmageed ZY, Nair D, Partyka MI, Kadowitz PJ, Belmadani S, Matrougui K (2010) Modified multipotent stromal cells with epidermal growth factor restore vasculogenesis and blood flow in ischemic hind-limb of type II diabetic mice. Lab Invest 90:985–996

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Austin S, St-Pierre J (2012) PGC1α and mitochondrial metabolism—emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 125:4963–4971

    Article  CAS  PubMed  Google Scholar 

  • Bellows CF, Zhang Y, Simmons PJ, Khalsa AS, Kolonin MG (2011) Influence of BMI on level of circulating progenitor cells. Obesity 19:1722–1726

    Article  PubMed Central  PubMed  Google Scholar 

  • Browning JD, Hort JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cardoso AR, Queliconi BB, Kowaltowski AJ (2010) Mitochondrial ion transport pathways: role in metabolic diseases. Biochim Biophys Acta 1797:832–838

    Article  CAS  PubMed  Google Scholar 

  • Carvalho SN, Lira DC, Oliveira GP, Thole AA, Stumbo AC, Caetano CE, Marques RG, Carvalho L (2010) Decreased collagen types I and IV, laminin, CK-19 and α-SMA expression after bone marrow cell transplantation in rats with liver fibrosis. Histochem Cell Biol 134:493–502

    Article  CAS  PubMed  Google Scholar 

  • Chan ME, Adler BJ, Green DE, Rubin CT (2012) Bone structure and B-cell populations, crippled by obesity, are partially rescued by brief daily exposure to low-magnitude mechanical signals. FASEB J 26:4855–4863

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH (2008) Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells 26:960–968

    Article  CAS  PubMed  Google Scholar 

  • Chung S, Dzeja PP, Faustino RS, Perez-Terzic C, Behfar A, Terzic A (2007) Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nat Clin Pract Cardiovasc Med 4:S60–S67

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cortez E, Neves FA, Bernardo AF, Stumbo AC, Carvalho L, Garcia-Souza E, Sichieri R, Moura AS (2012) Lymphocytes mitochondrial physiology as biomarker of energy metabolism during fasted and fed conditions. ScientificWorldJournal 2012:629326

    Article  PubMed Central  PubMed  Google Scholar 

  • Cortez M, Carmo LS, Rogero MM, Borelli P, Fock RA (2013) A high-fat diet increases IL-1, IL-6, and TNF-α production by increasing NF-κB and attenuating PPAR-γ expression in bone marrow mesenchymal stem cells. Inflammation 36:379–386

    Article  CAS  PubMed  Google Scholar 

  • Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778

    Article  CAS  PubMed  Google Scholar 

  • Gnacińska M, Małgorzewicz S, Stojek M, Łysiak-Szydłowska W, Sworczak K (2009) Role of adipokines in complications related to obesity: a review. Adv Med Sci 54:150–157

    PubMed  Google Scholar 

  • Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445

    Article  CAS  PubMed  Google Scholar 

  • Handschin C, Spiegelman BM (2006) Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27:728–735

    Article  CAS  PubMed  Google Scholar 

  • Juliusson G, Lenkei R, Liliemark J (1994) Flow cytometry of blood and bone marrow cells from patients with hairy cell leukemia: phenotype of hairy cells and lymphocyte subsets after treatment with 2-chlorodeoxyadenosine. Blood 12:3672–3681

    Google Scholar 

  • Lee MO (1929) Determination of the surface area of thewhite rat with application to the expressionof metabolic results.Am J Physiol89:24–33

    Google Scholar 

  • Lonergan T, Brenner C, Bavister B (2006) Differentiation-related changes in mitochondrial properties as indicators of stem cell competence. J Cell Physiol 208:149–153

    Article  CAS  PubMed  Google Scholar 

  • Lonergan T, Bavister B, Brenner C (2007) Mitochondria in stem cells. Mitochondrion 7:289–296

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mailloux RJ, Harper ME (2012) Mitochondrial proticity and ROS signaling: lessons from the uncoupling proteins. Trends Endocrinol Metab 23:451–458

    Article  CAS  PubMed  Google Scholar 

  • McGuire TR, Brusnahan SK, Bilek LD, Jackson JD, Kessinger MA, Berger AM, Garvin KL, O'Kane BJ, Tuljapurkar SR, Sharp JG (2011) Inflammation associated with obesity: relationship with blood and bone marrow endothelial cells. Obesity (Silver Spring) 19:2130–2136

    Article  CAS  Google Scholar 

  • Nesti C, Pasquali L, Vaglini F, Siciliano G, Murri L (2007) The role of mitochondria in stem cell biology. Biosci Rep 27:165–171

    Article  CAS  PubMed  Google Scholar 

  • Neves FA, Cortez E, Bernardo AF, Mattos AB, Vieira AK, Malafaia Tde O, Thole AA, Rodrigues-Cunha AC, Garcia-Souza EP, Sichieri R, Moura AS (2013) Heart energy metabolism impairment in Western-diet induced obese mice. J Nutr Biochem 25:50–57

    Article  PubMed  Google Scholar 

  • Ogawa M (1993) Differentiation and proliferation of hematopoietic stem cells. Blood 81:2844–2853

    CAS  PubMed  Google Scholar 

  • Paul F, Virgo PF, Gibbs GJ (2012) Flow cytometry in clinical pathology. Ann Clin Biochem 49:17–28

    Article  Google Scholar 

  • Piccoli C, Ria R, Scrima R, Cela O, D'Aprile A, Boffoli D, Falzetti F, Tabilio A, Capitanio N (2005) Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P)H oxidase activity. J Biol Chem 280:26467–26476

    Article  CAS  PubMed  Google Scholar 

  • Pietilä M, Palomäki S, Lehtonen S, Ritamo I, Valmu L, Nystedt J, Laitinen S, Leskelä HV, Sormunen R, Pesälä J, Nordström K, Vepsäläinen A, Lehenkari P (2012) Mitochondrial function and energy metabolism in umbilical cord blood- and bone marrow-derived mesenchymal stem cells. Stem Cells Dev 21:575–588

    Article  PubMed Central  PubMed  Google Scholar 

  • Popkin BM (2011) Contemporary nutritional transition: determinants of diet and its impact on body composition. Proc Nutr Soc 1:82–91

    Article  Google Scholar 

  • Popkin BM, Adair LS, NG SW (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 1:3–21

    Article  Google Scholar 

  • Rehman J (2010) Empowering self-renewal and differentiation: the role of mitochondria in stem cells. J Mol Med 88:981–986

    Article  PubMed Central  PubMed  Google Scholar 

  • Schiff M, Bénit P, Coulibaly A, Loublier S, El-Khoury R, Rustin P (2011) Mitochondrial response to controlled nutrition in health and disease. Nutr Rev 69:65–75

    Article  PubMed  Google Scholar 

  • Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle B, Mietus-Snyder ML, American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, Council on Nutrition, Physical Activity, and Metabolism (2009) Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 4:628–47

    Article  Google Scholar 

  • Thole AA, Rodrigues-Cunha AC, Carvalho SN, Garcia-Souza EP, Cortez E, Stumbo AC, Carvalho L, Moura AS (2012) Progenitor cells and TNF-alpha involvement during morphological changes in pancreatic islets of obese mice. Tissue Cell 44:238–248

    Article  CAS  PubMed  Google Scholar 

  • Trottier MD, Naaz A, Li Y, Fraker PJ (2012) Enhancement of hematopoiesis and lymphopoiesis in diet-induced obese mice. Proc Natl Acad Sci U S A 109:7622–7629

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tsai TH, Chai HT, Sun CK, Yen CH, Leu S, Chen YL, Chung SY, Ko SF, Chang HW, Wu CJ, Yip HK (2012) Obesity suppresses circulating level and function of endothelial progenitor cells and heart function. J Transl Med 10:137

    Article  PubMed Central  PubMed  Google Scholar 

  • Vachharajani V, Granger DN (2009) Adipose tissue: a motor for the inflammation associated with obesity. IUBMB Life 4:424–430

    Article  Google Scholar 

  • Wagner IJ, Szpalski C, Allen RJ Jr, Davidson EH, Canizares O, Saadeh PB, Warren SM (2012) Obesity impairs wound closure through a vasculogenic mechanism. Wound Repair Regen 20:512–522

    PubMed  Google Scholar 

  • Woo M, Isganaitis E, Cerletti M, Fitzpatrick C, Wagers AJ, Jimenez-Chillaron J, Patti ME (2011) Early life nutrition modulates muscle stem cell number: implications for muscle mass and repair. Stem Cells Dev 20:1763–1769

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wu CL, Diekman BO, Jain D, Guilak F (2013) Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fad pad: the effects of free fatty acids. Int J Obes (Lond) 37:1079–1087

    Article  CAS  Google Scholar 

  • Zalesin KC, Franklin BA, Miller WM, Peterson ED, McCullough PA (2011) Impact of obesity on cardiovascular disease. Med Clin North Am 5:919–937

    Article  Google Scholar 

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Authors and Affiliations

  1. 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

    Genilza Pereira de Oliveira, Erika Cortez, Simone Nunes de Carvalho, Laís Carvalho & Alessandra Alves Thole

  2. Laboratory of Physiology of Nutrition and Development, Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil

    Erika Cortez, Fabiana Alves Neves, Amélia Faustino Bernardo & Anibal Sanchez Moura

  3. Laboratory of Applied Immunology and Biochemistry of Proteins and Natural Products, Department of Biochemistry, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil

    Graça Justo Araujo & Katia Costa de Carvalho Sabino

Authors
  1. Genilza Pereira de Oliveira
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  2. Erika Cortez
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  3. Graça Justo Araujo
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  4. Katia Costa de Carvalho Sabino
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  5. Fabiana Alves Neves
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  6. Amélia Faustino Bernardo
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  7. Simone Nunes de Carvalho
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  8. Anibal Sanchez Moura
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  9. Laís Carvalho
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  10. Alessandra Alves Thole
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Corresponding author

Correspondence to Alessandra Alves Thole.

Additional information

This work was supported by the Foundation for Research of Rio de Janeiro (FAPERJ).

All authors interpreted the data and wrote the manuscript.

The authors declare no personal conflicts of interest.

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de Oliveira, G.P., Cortez, E., Araujo, G.J. et al. Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice. Cell Tissue Res 357, 185–194 (2014). https://doi.org/10.1007/s00441-014-1857-1

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  • DOI: https://doi.org/10.1007/s00441-014-1857-1

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