Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice
- 317 Downloads
- 4 Citations
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.
Keywords
Bone marrow cells High-fat diet Mitochondria Obesity Oxidative phosphorylationReferences
- 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 90:985–996PubMedCentralPubMedCrossRefGoogle Scholar
- Austin S, St-Pierre J (2012) PGC1α and mitochondrial metabolism—emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 125:4963–4971PubMedCrossRefGoogle Scholar
- Bellows CF, Zhang Y, Simmons PJ, Khalsa AS, Kolonin MG (2011) Influence of BMI on level of circulating progenitor cells. Obesity 19:1722–1726PubMedCentralPubMedCrossRefGoogle Scholar
- Browning JD, Hort JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152PubMedCentralPubMedCrossRefGoogle Scholar
- Cardoso AR, Queliconi BB, Kowaltowski AJ (2010) Mitochondrial ion transport pathways: role in metabolic diseases. Biochim Biophys Acta 1797:832–838PubMedCrossRefGoogle 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 134:493–502PubMedCrossRefGoogle 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 26:4855–4863PubMedCentralPubMedCrossRefGoogle 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 26:960–968PubMedCrossRefGoogle 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–S67PubMedCentralPubMedCrossRefGoogle 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 2012:629326PubMedCentralPubMedCrossRefGoogle 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 36:379–386PubMedCrossRefGoogle Scholar
- Fuchs E, Tumbar T, Guasch G (2004) Socializing with the neighbors: stem cells and their niche. Cell 116:769–778PubMedCrossRefGoogle 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 54:150–157PubMedGoogle Scholar
- Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445PubMedCrossRefGoogle Scholar
- Handschin C, Spiegelman BM (2006) Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27:728–735PubMedCrossRefGoogle 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 12:3672–3681Google Scholar
- Lee MO (1929) Determination of the surface area of thewhite rat with application to the expressionof metabolic results.Am J Physiol89:24–33Google Scholar
- Lonergan T, Brenner C, Bavister B (2006) Differentiation-related changes in mitochondrial properties as indicators of stem cell competence. J Cell Physiol 208:149–153PubMedCrossRefGoogle Scholar
- Lonergan T, Bavister B, Brenner C (2007) Mitochondria in stem cells. Mitochondrion 7:289–296PubMedCentralPubMedCrossRefGoogle Scholar
- Mailloux RJ, Harper ME (2012) Mitochondrial proticity and ROS signaling: lessons from the uncoupling proteins. Trends Endocrinol Metab 23:451–458PubMedCrossRefGoogle 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) 19:2130–2136CrossRefGoogle Scholar
- Nesti C, Pasquali L, Vaglini F, Siciliano G, Murri L (2007) The role of mitochondria in stem cell biology. Biosci Rep 27:165–171PubMedCrossRefGoogle 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 25:50–57PubMedCrossRefGoogle Scholar
- Ogawa M (1993) Differentiation and proliferation of hematopoietic stem cells. Blood 81:2844–2853PubMedGoogle Scholar
- Paul F, Virgo PF, Gibbs GJ (2012) Flow cytometry in clinical pathology. Ann Clin Biochem 49:17–28CrossRefGoogle 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 280:26467–26476PubMedCrossRefGoogle 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 21:575–588PubMedCentralPubMedCrossRefGoogle Scholar
- Popkin BM (2011) Contemporary nutritional transition: determinants of diet and its impact on body composition. Proc Nutr Soc 1:82–91CrossRefGoogle Scholar
- Popkin BM, Adair LS, NG SW (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 1:3–21CrossRefGoogle Scholar
- Rehman J (2010) Empowering self-renewal and differentiation: the role of mitochondria in stem cells. J Mol Med 88:981–986PubMedCentralPubMedCrossRefGoogle 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 69:65–75PubMedCrossRefGoogle 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 4:628–47CrossRefGoogle 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 44:238–248PubMedCrossRefGoogle 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 109:7622–7629PubMedCentralPubMedCrossRefGoogle 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 10:137PubMedCentralPubMedCrossRefGoogle Scholar
- Vachharajani V, Granger DN (2009) Adipose tissue: a motor for the inflammation associated with obesity. IUBMB Life 4:424–430CrossRefGoogle 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 20:512–522PubMedGoogle 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 20:1763–1769PubMedCentralPubMedCrossRefGoogle 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) 37:1079–1087CrossRefGoogle Scholar
- Zalesin KC, Franklin BA, Miller WM, Peterson ED, McCullough PA (2011) Impact of obesity on cardiovascular disease. Med Clin North Am 5:919–937CrossRefGoogle Scholar