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Stem Cell and Obesity: Current State and Future Perspective

  • Moloud Payab
  • Parisa Goodarzi
  • Najmeh Foroughi Heravani
  • Mahdieh Hadavandkhani
  • Zeinab Zarei
  • Khadijeh Falahzadeh
  • Bagher Larijani
  • Fakher Rahim
  • Babak Arjmand
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1089)

Abstract

Obesity as a worldwide growing challenge is determined by abnormal fat deposition, which may damage general health. Weight loss and control of related risk factors like type2 diabetes, dyslipidemia, hypertension, cardiovascular diseases, and metabolic syndrome is an important concern in obesity management. Different therapeutic approaches such as lifestyle change, medications, and surgery are introduced for obesity treatment. Despite of gaining partially desirable results, the problem is remained unsolved. Therefore, finding a new approach that can overcome previous limitations is very attractive for both researchers and clinicians. Cell-based therapy using adipose-derived stromal cells seems to be a promising strategy to control obesity and related syndromes. To attain this aim, understanding of different type of adipose tissues, main signaling pathways, and different factors involved in development of adipocyte is essential. Recently, several cell-based methods like stem cell administration, brown adipose tissue transplantation, cell lysates and exosomes have been examined on obese mouse models to manage obesity and related disorders. Successful outcome of such preclinical studies can encourage the cell-based clinical trials in the near future.

Keywords

Adipocyte Adipose tissue Animal models Cell therapy Mesenchymal stem/stromal cells Obesity 

Abbreviations

ADAMTS5

A disintegrin and metalloproteinase with thrombospondin motif 5

ADSC

Adipose derived mesenchymal stem cells

AKR1B10

Aldo-keto reductase family 1 member B10

aP2

Adipocyte protein 2

ASCs

Adipose derived-stem cells

BAT

Brown adipose tissue

BMI

Body mass index

BM-MSCs

Bone marrow mesenchymal stem cells

BMP4

Bone morphogenic protein 4

C/EBP α (A)/β/δ

CCAAT/enhancer-binding protein α/β/δ

CB-MSC

Umbilical cord blood-mesenchymal stem cell

CB-plasma

Cord blood plasma

CD24

Cluster of differentiation 24

Cidea

Cell death-inducing DFFA-like effector a

CIT

Cold induced thermogenesis

Cox2

Cyclooxygenase 2

CRE

cAMP response element

CXCL3

Chemokine(C-X-C motif) ligand3

DIO

Diet-induced obese

DIT

Diet-induced thermogenesis

Dlk1

Delta like non-canonical notch ligand 1

EBF2

Early B cell factor 2

EHMT1

Euchromatic histone lysine methyltransferase 1

ENG

Endoglin (protein)

ERK

Extra cellular receptor kinase

ES

Embryonic stem cell

EVs

Extracellular vesicles

FDA

Food and drug administration

FGF10

Fibroblast growth factor 10

FPG

Fasting plasma glucose

FTO

Fat mass and obesity associated(gene)

H3K9

Histone H3 lysine 9

HDL

High-density lipoprotein

HFD

High-fat diet

Hh

Hedgehog

HOXC8

HomeoboxC8

IDF

International diabetes federation

IGF1

Insulin-like growth factor1

IL6

Interlukine 6

LOX

lysyl oxidase

M-BA

MSC-derived BAT

Mef2

Myocyte enhancer factor 2

miR-196a

MicroRNA 196a

miRNAs

MicroRNAs

MSC

Mesenchymal stem cells

Myf5

Myogenic factor 5

NICD

Notch intracellular domain

NRs

Number of nuclear receptors

Pax7

Paired box 7

PDGF

Platelet-derived growth factor

PDGPR α /b

Platelet derived growth factor receptor α/β

PGCα

Peroxisome proliferator-activated receptor-gamma coactivator α

PLIN

Perilipin

PPAR-γ/G

Peroxisome proliferator-activated receptor-γ

PPRE

PPAR response element

PRb/Rb

Retinoblastoma protein/ retinoblastoma

PRDM16

PR domain containing 16

PREF1

Preadipocyte factor 1

RARE

Retinoic acid response element

RIP

Receptor interacting protein

SAT

Subcutaneus white adipose tissue

SMA

Spinal muscular atrophy

STAT3

Signal transducers and activators of transcription 3

TC1

Immune response regulator

TNFα

Tumor necrosis factor α

TRE

Thyroid response element

TGFβ

Transforming growth factor beta

UCP1

Uncoupling protein 1

VAT

Visceral white adipose tissue

VEAT

Visceral endothelial adipose tissue

WAT

White adipose tissue

WHO

World health organization

Wisp2

Inducible signaling path-way protein 2

WNT1

Wingless-type MMTV integration family member 1

Zfp516

Zinc finger protein 516

P107

Retinoblastoma-like 1

Notes

Acknowledgement

The authors would like to acknowledge Rasta Arjmand for her assistance in figure design. We also thank Dr. Mohsen khorshidi, and Maryam Afshari for their kind support.

References

  1. Abdesselem H, Madani A, Hani A, Al-Noubi M, Goswami N, Hamidane HB, Billing AM, Pasquier J, Bonkowski MS, Halabi N (2016) SIRT1 limits adipocyte hyperplasia through c-Myc inhibition. J Biol Chem 291:2119–2135CrossRefPubMedGoogle Scholar
  2. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822CrossRefPubMedGoogle Scholar
  3. Aghayan HR, Goodarzi P, Arjmand B (2015) GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular therapy. Methods Mol Biol 1283:93–107CrossRefPubMedGoogle Scholar
  4. Aghayan HR, Arjmand B, Ahmadbeigi N, Gheisari Y, Vasei M (2017) Draft of Iranian National Guideline for cell therapy manufacturing. Arch Iran Med 20:547–550PubMedGoogle Scholar
  5. Aldiss P, Davies G, Woods R, Budge H, Sacks HS, Symonds ME (2017) ‘Browning’ the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk. Int J Cardiol 228:265–274PubMedCentralCrossRefPubMedGoogle Scholar
  6. Ali AT, Hochfeld WE, Myburgh R, Pepper MS (2013) Adipocyte and adipogenesis. Eur J Cell Biol 92:229–236CrossRefPubMedGoogle Scholar
  7. Alkhalil M, Smajilagic A, Redzic A (2015) Human dental pulp mesenchymal stem cells isolation and osteoblast differentiation. Med Glas (Zenica) 12:27–32Google Scholar
  8. Anderson JW, Kendall CW, Jenkins DJ (2003) Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr 22:331–339CrossRefPubMedGoogle Scholar
  9. Augello A, De Bari C (2010) The regulation of differentiation in mesenchymal stem cells. Hum Gene Ther 21:1226–1238CrossRefPubMedGoogle Scholar
  10. Baksh D, Song L, Tuan R (2004) Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J Cell Mol Med 8:301–316CrossRefPubMedGoogle Scholar
  11. Baptista LS, Silva KR, Borojevic R (2015) Obesity and weight loss could alter the properties of adipose stem cells? World J Stem Cells 7:165–173PubMedCentralCrossRefPubMedGoogle Scholar
  12. Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, Giacobino JP, De Matteis R, Cinti S (2010) The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 298:E1244–E1253CrossRefPubMedGoogle Scholar
  13. Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, Eychmuller A, Gordts PL, Rinninger F, Bruegelmann K, Freund B, Nielsen P, Merkel M, Heeren J (2011) Brown adipose tissue activity controls triglyceride clearance. Nat Med 17:200–205CrossRefPubMedGoogle Scholar
  14. Berkowitz DE, Brown D, Lee KM, Emala C, Palmer D, An Y, Breslow M (1998) Endotoxin-induced alteration in the expression of leptin and beta3-adrenergic receptor in adipose tissue. Am J Phys 274:E992–E997CrossRefGoogle Scholar
  15. Bianco P (2014) “Mesenchymal” stem cells. Annu Rev Cell Dev Biol 30:677–704CrossRefPubMedGoogle Scholar
  16. Bilkovski R, Schulte DM, Oberhauser F, Gomolka M, Udelhoven M, Hettich MM, Roth B, Heidenreich A, Gutschow C, Krone W (2010) Role of WNT-5a in the determination of human mesenchymal stem cells into preadipocytes. J Biol Chem 285:6170–6178CrossRefPubMedGoogle Scholar
  17. Boucher J, Softic S, EL Ouaamari A, Krumpoch MT, Kleinridders A, Kulkarni RN, O'neill BT, Kahn CR (2016) Differential roles of insulin and IGF-1 receptors in adipose tissue development and function. Diabetes 65:2201–2213PubMedCentralCrossRefPubMedGoogle Scholar
  18. Brand MD, Pakay JL, Ocloo A, Kokoszka J, Wallace DC, Brookes PS, Cornwall EJ (2005) The basal proton conductance of mitochondria depends on adenine nucleotide translocase content. Biochem J 392:353–362PubMedCentralCrossRefPubMedGoogle Scholar
  19. Cao H, Gerhold K, Mayers JR, Wiest MM, Watkins SM, Hotamisligil GS (2008) Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 134:933–944PubMedCentralCrossRefPubMedGoogle Scholar
  20. Cao M, Pan Q, Dong H, Yuan X, Li Y, Sun Z, Dong X, Wang H (2015) Adipose-derived mesenchymal stem cells improve glucose homeostasis in high-fat diet-induced obese mice. Stem Cell Res Ther 6:208PubMedCentralCrossRefPubMedGoogle Scholar
  21. Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084CrossRefPubMedGoogle Scholar
  22. Carey AL, Febbraio MA (2004) Interleukin-6 and insulin sensitivity: friend or foe? Diabetologia 47:1135–1142CrossRefPubMedGoogle Scholar
  23. Chatzistamatiou TK, Papassavas AC, Michalopoulos E, Gamaloutsos C, Mallis P, Gontika I, Panagouli E, Koussoulakos SL, Stavropoulos-Giokas C (2014) Optimizing isolation culture and freezing methods to preserve Wharton's jelly's mesenchymal stem cell (MSC) properties: an MSC banking protocol validation for the Hellenic Cord Blood Bank. Transfusion 54:3108–3120CrossRefPubMedGoogle Scholar
  24. Chen M-H, Tong Q (2013) An update on the regulation of adipogenesis. Drug Discov Today: Dis Mech 10:e15–e19CrossRefGoogle Scholar
  25. Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, Cao J, Xie N, Velletri T, Zhang X (2016) Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death Differ 23:1128PubMedCentralCrossRefPubMedGoogle Scholar
  26. Cleal L, Aldea T, Chau YY (2017) Fifty shades of white: understanding heterogeneity in white adipose stem cells. Adipocytes 6:205–216CrossRefGoogle Scholar
  27. Cypess AM, Kahn CR (2010) Brown fat as a therapy for obesity and diabetes. Curr Opin Endocrinol Diabetes Obes 17:143–149PubMedCentralCrossRefPubMedGoogle Scholar
  28. Esteve Rafols M (2014) Adipose tissue: cell heterogeneity and functional diversity. Endocrinol Nutr 61:100–112CrossRefPubMedGoogle Scholar
  29. Ferrannini E, Camastra S (1998) Relationship between impaired glucose tolerance, non-insulin-dependent diabetes mellitus and obesity. Eur J Clin Investig 28(Suppl 2):3–6 discussion 6-7CrossRefGoogle Scholar
  30. Feve B (2013) Adiponectin: an anti-carcinogenic adipokine? Ann Endocrinol (Paris) 74:102–105CrossRefGoogle Scholar
  31. Fontaine C, Cousin W, Plaisant M, Dani C, Peraldi P (2008) Hedgehog signaling alters adipocyte maturation of human mesenchymal stem cells. Stem Cells 26:1037–1046CrossRefPubMedGoogle Scholar
  32. Fruhbeck G, Becerril S, Sainz N, Garrastachu P, Garcia-Velloso MJ (2009) BAT: a new target for human obesity? Trends Pharmacol Sci 30:387–396CrossRefPubMedGoogle Scholar
  33. Gao X, Salomon C, Freeman DJ (2017) Extracellular vesicles from adipose tissue-a potential role in obesity and type 2 diabetes? Front Endocrinol (Lausanne) 8:202CrossRefGoogle Scholar
  34. Gao Y, Vidal-Itriago A, Milanova I, Korpel NL, Kalsbeek MJ, Tom RZ, Kalsbeek A, Hofmann SM, Yi CX (2018) Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase. Mol Metab 7:155–160CrossRefPubMedGoogle Scholar
  35. Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5:362–369CrossRefPubMedGoogle Scholar
  36. Gori F, Thomas T, Hicok KC, Spelsberg TC, Riggs BL (1999) Differentiation of human marrow stromal precursor cells: bone morphogenetic Protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation. J Bone Miner Res 14:1522–1535CrossRefPubMedGoogle Scholar
  37. Guo L, Li X, Tang Q-Q (2015) Transcriptional regulation of adipocyte differentiation: a central role for CCAAT/enhancer-binding protein (C/EBP) β. J Biol Chem 290:755–761CrossRefPubMedGoogle Scholar
  38. Halse R, Pearson SL, Mccormack JG, Yeaman SJ, Taylor R (2001) Effects of tumor necrosis factor-alpha on insulin action in cultured human muscle cells. Diabetes 50:1102–1109PubMedCentralCrossRefPubMedGoogle Scholar
  39. Hammarstedt A, Hedjazifar S, Jenndahl L, Gogg S, Grunberg J, Gustafson B, Klimcakova E, Stich V, Langin D, Laakso M, Smith U (2013) WISP2 regulates preadipocyte commitment and PPARgamma activation by BMP4. Proc Natl Acad Sci U S A 110:2563–2568PubMedCentralCrossRefPubMedGoogle Scholar
  40. Han Y-F, Tao R, Sun T-J, Chai J-K, Xu G, Liu J (2013) Optimization of human umbilical cord mesenchymal stem cell isolation and culture methods. Cytotechnology 65:819–827PubMedCentralCrossRefPubMedGoogle Scholar
  41. Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252CrossRefPubMedGoogle Scholar
  42. Herrera BM, Keildson S, Lindgren CM (2011) Genetics and epigenetics of obesity. Maturitas 69:41–49PubMedCentralCrossRefPubMedGoogle Scholar
  43. Hu E, Tontonoz P, Spiegelman BM (1995) Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha. Proc Natl Acad Sci U S A 92:9856–9860PubMedCentralCrossRefPubMedGoogle Scholar
  44. Huang H, Song T-J, Li X, Hu L, He Q, Liu M, Lane MD, Tang Q-Q (2009) BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci 106:12670–12675CrossRefPubMedGoogle Scholar
  45. Ikeda K, Maretich P, Kajimura S (2018) The common and distinct features of Brown and Beige adipocytes. Trends Endocrinol Metab 29:191–200CrossRefPubMedGoogle Scholar
  46. Illouz Y-G, Sterodimas A, Green A C (2011) Role of adipose stem cells therapy in obesity. 133–139Google Scholar
  47. Jafari-Adli S, Jouyandeh Z, Qorbani M, Soroush A, Larijani B, Hasani-Ranjbar S (2014) Prevalence of obesity and overweight in adults and children in Iran; a systematic review. J Diabetes Metab Disord 13:121PubMedCentralCrossRefPubMedGoogle Scholar
  48. James AW (2013) Review of signaling pathways governing MSC osteogenic and Adipogenic differentiation. Scientifica (Cairo) 2013:684736Google Scholar
  49. Jang H, Kim M, Lee S, Kim J, Woo D-C, Kim KW, Song K, Lee I (2016) Adipose tissue hyperplasia with enhanced adipocyte-derived stem cell activity in Tc1(C8orf4)-deleted mice. Sci Rep 6:35884PubMedCentralCrossRefPubMedGoogle Scholar
  50. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, Cushman SW, Periwal V (2009) Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLoS Comput Biol 5:e1000324PubMedCentralCrossRefPubMedGoogle Scholar
  51. Joe AW, Yi L, Even Y, Vogl AW, Rossi FM (2009) Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet. Stem Cells 27:2563–2570CrossRefPubMedGoogle Scholar
  52. Karagianni M, Brinkmann I, Kinzebach S, Grassl M, Weiss C, Bugert P, Bieback K (2013) A comparative analysis of the adipogenic potential in human mesenchymal stromal cells from cord blood and other sources. Cytotherapy 15:76–88CrossRefPubMedGoogle Scholar
  53. Kawai M, Mushiake S, Bessho K, Murakami M, Namba N, Kokubu C, Michigami T, Ozono K (2007) Wnt/Lrp/β-catenin signaling suppresses adipogenesis by inhibiting mutual activation of PPARγ and C/EBPα. Biochem Biophys Res Commun 363:276–282CrossRefPubMedGoogle Scholar
  54. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W (2004) Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10:625–632CrossRefPubMedGoogle Scholar
  55. Kopan R, Ilagan MXG (2009) The canonical notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233PubMedCentralCrossRefPubMedGoogle Scholar
  56. Kusuyama J, Komorizono A, Bandow K, Ohnishi T, Matsuguchi T (2016) CXCL3 positively regulates adipogenic differentiation. J Lipid Res 57:1806–1820PubMedCentralCrossRefPubMedGoogle Scholar
  57. Lagathu C, Christodoulides C, Tan CY, Virtue S, Laudes M, Campbell M, Ishikawa K, Ortega F, Tinahones FJ, Fernández-Real J-M (2010) Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity. Int J Obes 34:1695CrossRefGoogle Scholar
  58. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US, Kebebew E, Pacak K, Chen KY, Celi FS (2014) Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 19:302–309CrossRefPubMedGoogle Scholar
  59. Lee CW, Hsiao WT, Lee OK (2017) Mesenchymal stromal cell-based therapies reduce obesity and metabolic syndromes induced by a high-fat diet. Transl Res 182:61–74.e8CrossRefPubMedGoogle Scholar
  60. Lehr S, Hartwig S, Sell H (2012) Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl 6:91–101CrossRefPubMedGoogle Scholar
  61. Li H, Li T, Wang S, Wei J, Fan J, Li J, Han Q, Liao L, Shao C, Zhao RC (2013) miR-17-5p and miR-106a are involved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells. Stem Cell Res 10:313–324CrossRefPubMedGoogle Scholar
  62. Lidell ME, Betz MJ, Leinhard OD, Heglind M, Elander L, Slawik M, Mussack T, Nilsson D, Romu T, Nuutila P, Virtanen KA, Beuschlein F, Persson A, Borga M, Enerbäck S (2013) Evidence for two types of brown adipose tissue in humans. Nat Med 19:631CrossRefPubMedGoogle Scholar
  63. Lien CC, Jiang JL, Jian DY, Kwok CF, Ho LT, Juan CC (2016) Chronic endothelin-1 infusion causes adipocyte hyperplasia in rats. Obesity 24:643–653CrossRefPubMedGoogle Scholar
  64. Lin F-T, Lane MD (1994) CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program. Proc Natl Acad Sci 91:8757–8761CrossRefPubMedGoogle Scholar
  65. Liu J, Farmer SR (2004) Regulating the balance between peroxisome proliferator-activated receptor γ and β-catenin signaling during Adipogenesis A glycogen synthase kinase 3β phosphorylation-defective mutant of β-catenin inhibits EXPRESSION of a subset of adipogenic genes. J Biol Chem 279:45020–45027CrossRefPubMedGoogle Scholar
  66. Liu X, Wang S, You Y, Meng M, Zheng Z, Dong M, Lin J, Zhao Q, Zhang C, Yuan X, Hu T, Liu L, Huang Y, Zhang L, Wang D, Zhan J, Jong Lee H, Speakman JR, Jin W (2015) Brown adipose tissue transplantation reverses obesity in Ob/Ob mice. Endocrinology 156:2461–2469CrossRefPubMedGoogle Scholar
  67. Liu GY, Liu J, Wang YL, Liu Y, Shao Y, Han Y, Qin YR, Xiao FJ, Li PF, Zhao LJ, Gu EY, Chen SY, Gao LH, Wu CT, Hu XW, Duan HF (2016) Adipose-derived mesenchymal stem cells ameliorate lipid metabolic disturbance in mice. Stem Cells Transl Med 5:1162–1170PubMedCentralCrossRefPubMedGoogle Scholar
  68. Lopatina T, Bruno S, Tetta C, Kalinina N, Porta M, Camussi G (2014) Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Communication and Signaling : CCS 12:26–26CrossRefGoogle Scholar
  69. Matsushita K (2016) Mesenchymal stem cells and metabolic syndrome: current understanding and potential clinical implications. Stem Cells Int 2016:10CrossRefGoogle Scholar
  70. Matsushita K, Dzau VJ (2017) Mesenchymal stem cells in obesity: insights for translational applications. Lab Investig 97:1158CrossRefPubMedGoogle Scholar
  71. Ming Shi XC, Blair H, Yang X, Mcdonald J, Cao X (2000) Tandem repeat of C/EBP binding sites mediates PPARγ2 gene transcription in glucocorticoid-induced adipocyte differentiationGoogle Scholar
  72. Mori M, Nakagami H, Rodriguez-Araujo G, Nimura K, Kaneda Y (2012) Essential role for miR-196a in brown adipogenesis of white fat progenitor cells. PLoS Biol 10:e1001314PubMedCentralCrossRefPubMedGoogle Scholar
  73. Narayanaswami V, Dwoskin LP (2017) Obesity: current and potential pharmacotherapeutics and targets. Pharmacol Ther 170:116–147CrossRefPubMedGoogle Scholar
  74. Nerlov C (2007) The C/EBP family of transcription factors: a paradigm for interaction between gene expression and proliferation control. Trends Cell Biol 17:318–324CrossRefPubMedGoogle Scholar
  75. Nishimura S, Manabe I, Nagasaki M, Hosoya Y, Yamashita H, Fujita H, Ohsugi M, Tobe K, Kadowaki T, Nagai R, Sugiura S (2007) Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 56:1517–1526CrossRefPubMedGoogle Scholar
  76. Payab M, Hasani-Ranjbar S, Larijani B (2014) Whether all obese subjects both in metabolic groups and non-metabolic groups should be treated or not. J Diabetes Metab Disord 13:21–21PubMedCentralCrossRefPubMedGoogle Scholar
  77. Payab M, Amoli MM, Qorbani M, Hasani-Ranjbar S (2017a) Adiponectin gene variants and abdominal obesity in an Iranian population. Eat Weight Disord – Studies on Anorexia, Bulimia and Obesity 22:85–90CrossRefGoogle Scholar
  78. Payab M, Hasani-Ranjbar S, Merati Y, Esteghamati A, Qorbani M, Hematabadi M, Rashidian H, Shirzad N (2017b) The prevalence of metabolic syndrome and different obesity phenotype in Iranian male military personnel. Am J Mens Health 11:404–413CrossRefPubMedGoogle Scholar
  79. Pellegrinelli V, Carobbio S, Vidal-Puig A (2016) Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 59:1075–1088PubMedCentralCrossRefPubMedGoogle Scholar
  80. Penfornis P, Pochampally R (2011) Isolation and expansion of mesenchymal stem cells/multipotential stromal cells from human bone marrow. In: Mesenchymal stem cell assays and applications. Springer, ChamGoogle Scholar
  81. Perez LM, Suarez J, Bernal A, DE Lucas B, San Martin N, Galvez BG (2016) Obesity-driven alterations in adipose-derived stem cells are partially restored by weight loss. Obesity (Silver Spring) 24:661–669CrossRefGoogle Scholar
  82. Petroni ML, Caletti MT, Calugi S, Dalle Grave R, Marchesini G (2017) Long-term treatment of severe obesity: are lifestyle interventions still an option? Expert Rev Endocrinol Metabol 12:391–400CrossRefGoogle Scholar
  83. Pietrabissa G, Manzoni GM, Corti S, Vegliante N, Molinari E, Castelnuovo G (2012) Addressing motivation in Globesity treatment: a new challenge for clinical psychology. Front Psychol 3:317PubMedCentralCrossRefPubMedGoogle Scholar
  84. Pi-Sunyer X (2009) The medical risks of obesity. Postgrad Med 121:21–33PubMedCentralCrossRefPubMedGoogle Scholar
  85. Poher AL, Altirriba J, Veyrat-Durebex C, Rohner-Jeanrenaud F (2015) Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance. Front Physiol 6:4PubMedCentralCrossRefPubMedGoogle Scholar
  86. Pories WJ (2008) Bariatric surgery: risks and rewards. J Clin Endocrinol Metab 93:S89–S96PubMedCentralCrossRefPubMedGoogle Scholar
  87. Rabelo R, Reyes C, Schifman A, Silva JE (1996) Interactions among receptors, thyroid hormone response elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone. Endocrinology 137:3478–3487CrossRefPubMedGoogle Scholar
  88. Rieusset J, Touri F, Michalik L, Escher P, Desvergne B, Niesor E, Wahli W (2002) A new selective peroxisome proliferator-activated receptor gamma antagonist with antiobesity and antidiabetic activity. Mol Endocrinol 16:2628–2644CrossRefPubMedGoogle Scholar
  89. Rogers NH (2015) Brown adipose tissue during puberty and with aging. Ann Med 47:142–149CrossRefPubMedGoogle Scholar
  90. Rosell M, Jones MC, Parker MG (2011) Role of nuclear receptor corepressor RIP140 in metabolic syndrome. Biochim Biophys Acta 1812:919–928PubMedCentralCrossRefPubMedGoogle Scholar
  91. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM (1999) PPARγ is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4:611–617CrossRefPubMedGoogle Scholar
  92. Rosen ED, Hsu C-H, Wang X, Sakai S, Freeman MW, Gonzalez FJ, Spiegelman BM (2002) C/EBPα induces adipogenesis through PPARγ: a unified pathway. Genes Dev 16:22–26PubMedCentralCrossRefPubMedGoogle Scholar
  93. Rosenwald M, Perdikari A, Rülicke T, Wolfrum C (2013) Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 15:659CrossRefPubMedGoogle Scholar
  94. Rui L (2017) Brown and Beige adipose tissues in health and disease. Compr Physiol 7:1281–1306PubMedCentralCrossRefPubMedGoogle Scholar
  95. Sakurai T, Ogasawara J, Kizaki T, Ishibashi Y, Sumitani Y, Takahashi K, Ishida H, Miyazaki H, Saitoh D, Haga S, Izawa T, Ohno H (2012) Preventive and improvement effects of exercise training and supplement intake in white adipose tissues on obesity and lifestyle-related diseases. Environ Health Prev Med 17:348–356PubMedCentralCrossRefPubMedGoogle Scholar
  96. Sano S, Izumi Y, Yamaguchi T, Yamazaki T, Tanaka M, Shiota M, Osada-Oka M, Nakamura Y, Wei M, Wanibuchi H, Iwao H, Yoshiyama M (2014) Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1 cells. Biochem Biophys Res Commun 445:327–333CrossRefPubMedGoogle Scholar
  97. Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, Tavernier G, Langin D, Spiegelman BM (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6:38–54PubMedCentralCrossRefPubMedGoogle Scholar
  98. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454:961–967PubMedCentralCrossRefPubMedGoogle Scholar
  99. Shan T, Liu J, Wu W, Xu Z, Wang Y (2017) Roles of notch signaling in adipocyte progenitor cells and mature adipocytes. J Cell Physiol 232:1258–1261CrossRefPubMedGoogle Scholar
  100. Shang Q, Bai Y, Wang G, Song Q, Guo C, Zhang L, Wang Q (2015) Delivery of adipose-derived stem cells attenuates adipose tissue inflammation and insulin resistance in obese mice through remodeling macrophage phenotypes. Stem Cells Dev 24:2052–2064CrossRefPubMedGoogle Scholar
  101. Short B, Brouard N, Occhiodoro-Scott T, Ramakrishnan A, Simmons PJ (2003) Mesenchymal stem cells. Arch Med Res 34:565–571CrossRefGoogle Scholar
  102. Silva JE, Bianco SD (2008) Thyroid-adrenergic interactions: physiological and clinical implications. Thyroid 18:157–165CrossRefPubMedGoogle Scholar
  103. Song B-Q, Chi Y, Li X, Du W-J, Han Z-B, Tian J-J, Li J-J, Chen F, Wu H-H, Han L-X (2015) Inhibition of notch signaling promotes the adipogenic differentiation of mesenchymal stem cells through autophagy activation and PTEN-PI3K/AKT/mTOR pathway. Cell Physiol Biochem 36:1991–2002CrossRefPubMedGoogle Scholar
  104. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Lango Allen H, Lindgren CM, Luan J, Magi R, Randall JC, Vedantam S, Winkler TW, Qi L, Workalemahu T, Heid IM, Steinthorsdottir V, Stringham HM, Weedon MN, Wheeler E, Wood AR, Ferreira T, Weyant RJ, Segre AV, Estrada K, Liang L, Nemesh J, Park JH, Gustafsson S, Kilpelainen TO, Yang J, Bouatia-Naji N, Esko T, Feitosa MF, Kutalik Z, Mangino M, Raychaudhuri S, Scherag A, Smith AV, Welch R, Zhao JH, Aben KK, Absher DM, Amin N, Dixon AL, Fisher E, Glazer NL, Goddard ME, Heard-Costa NL, Hoesel V, Hottenga JJ, Johansson A, Johnson T, Ketkar S, Lamina C, Li S, Moffatt MF, Myers RH, Narisu N, Perry JR, Peters MJ, Preuss M, Ripatti S, Rivadeneira F, Sandholt C, Scott LJ, Timpson NJ, Tyrer JP, Van Wingerden S, Watanabe RM, White CC, Wiklund F, Barlassina C, Chasman DI, Cooper MN, Jansson JO, Lawrence RW, Pellikka N, Prokopenko I, Shi J, Thiering E, Alavere H, Alibrandi MT, Almgren P, Arnold AM, Aspelund T, Atwood LD, Balkau B, Balmforth AJ, Bennett AJ, Ben-Shlomo Y, Bergman RN, Bergmann S, Biebermann H, Blakemore AI, Boes T, Bonnycastle LL, Bornstein SR, Brown MJ, Buchanan TA, Busonero F, Campbell H, Cappuccio FP, Cavalcanti-Proenca C, Chen YD, Chen CM, Chines PS, Clarke R, Coin L, Connell J, Day IN, Den Heijer M, Duan J, Ebrahim S, Elliott P, Elosua R, Eiriksdottir G, Erdos MR, Eriksson JG, Facheris MF, Felix SB, Fischer-Posovszky P, Folsom AR, Friedrich N, Freimer NB, Fu M, Gaget S, Gejman PV, Geus EJ, Gieger C, Gjesing AP, Goel A, Goyette P, Grallert H, Grassler J, Greenawalt DM, Groves CJ, Gudnason V, Guiducci C, Hartikainen AL, Hassanali N, Hall AS, Havulinna AS, Hayward C, Heath AC, Hengstenberg C, Hicks AA, Hinney A, Hofman A, Homuth G, Hui J, Igl W, Iribarren C, Isomaa B, Jacobs KB, Jarick I, Jewell E, John U, Jorgensen T, Jousilahti P, Jula A, Kaakinen M, Kajantie E, Kaplan LM, Kathiresan S, Kettunen J, Kinnunen L, Knowles JW, Kolcic I, Konig IR, Koskinen S, Kovacs P, Kuusisto J, Kraft P, Kvaloy K, Laitinen J, Lantieri O, Lanzani C, Launer LJ, Lecoeur C, Lehtimaki T, Lettre G, Liu J, Lokki ML, Lorentzon M, Luben RN, Ludwig B, Manunta P, Marek D, Marre M, Martin NG, Mcardle WL, Mccarthy A, Mcknight B, Meitinger T, Melander O, Meyre D, Midthjell K, Montgomery GW, Morken MA, Morris AP, Mulic R, Ngwa JS, Nelis M, Neville MJ, Nyholt DR, O'donnell CJ, O'rahilly S, Ong KK, Oostra B, Pare G, Parker AN, Perola M, Pichler I, Pietilainen KH, Platou CG, Polasek O, Pouta A, Rafelt S, Raitakari O, Rayner NW, Ridderstrale M, Rief W, Ruokonen A, Robertson NR, Rzehak P, Salomaa V, Sanders AR, Sandhu MS, Sanna S, Saramies J, Savolainen MJ, Scherag S, Schipf S, Schreiber S, Schunkert H, Silander K, Sinisalo J, Siscovick DS, Smit JH, Soranzo N, Sovio U, Stephens J, Surakka I, Swift AJ, Tammesoo ML, Tardif JC, Teder-Laving M, Teslovich TM, Thompson JR, Thomson B, Tonjes A, Tuomi T, Van Meurs JB, Van Ommen GJ, Vatin V, Viikari J, Visvikis-Siest S, Vitart V, Vogel CI, Voight BF, Waite LL, Wallaschofski H, Walters GB, Widen E, Wiegand S, Wild SH, Willemsen G, Witte DR, Witteman JC, Xu J, Zhang Q, Zgaga L, Ziegler A, Zitting P, Beilby JP, Farooqi IS, Hebebrand J, Huikuri HV, James AL, Kahonen M, Levinson DF, Macciardi F, Nieminen MS, Ohlsson C, Palmer LJ, Ridker PM, Stumvoll M, Beckmann JS, Boeing H, Boerwinkle E, Boomsma DI, Caulfield MJ, Chanock SJ, Collins FS, Cupples LA, Smith GD, Erdmann J, Froguel P, Gronberg H, Gyllensten U, Hall P, Hansen T, Harris TB, Hattersley AT, Hayes RB, Heinrich J, Hu FB, Hveem K, Illig T, Jarvelin MR, Kaprio J, Karpe F, Khaw KT, Kiemeney LA, Krude H, Laakso M, Lawlor DA, Metspalu A, Munroe PB, Ouwehand WH, Pedersen O, Penninx BW, Peters A, Pramstaller PP, Quertermous T, Reinehr T, Rissanen A, Rudan I, Samani NJ, Schwarz PE, Shuldiner AR, Spector TD, Tuomilehto J, Uda M, Uitterlinden A, Valle TT, Wabitsch M, Waeber G, Wareham NJ, Watkins H, Wilson JF, Wright AF, Zillikens MC, Chatterjee N, Mccarroll SA, Purcell S, Schadt EE, Visscher PM, Assimes TL, Borecki IB, Deloukas P, Fox CS, Groop LC, Haritunians T, Hunter DJ, Kaplan RC, Mohlke KL, O'connell JR, Peltonen L, Schlessinger D, Strachan DP, Van Duijn CM, Wichmann HE, Frayling TM, Thorsteinsdottir U, Abecasis GR, Barroso I, Boehnke M, Stefansson K, North KE, Mccarthy MI, Hirschhorn JN, Ingelsson E, Loos RJ (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42:937–948PubMedCentralCrossRefPubMedGoogle Scholar
  105. Spinella-Jaegle S, Rawadi G, Kawai S, Gallea S, Faucheu C, Mollat P, Courtois B, Bergaud B, Ramez V, Blanchet AM (2001) Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation. J Cell Sci 114:2085–2094PubMedGoogle Scholar
  106. Stanford KI, Middelbeek RJ, Townsend KL, An D, Nygaard EB, Hitchcox KM, Markan KR, Nakano K, Hirshman MF, Tseng YH, Goodyear LJ (2013) Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 123:215–223CrossRefPubMedGoogle Scholar
  107. Suh JM, Gao X, Mckay J, Mckay R, Salo Z, Graff JM (2006) Hedgehog signaling plays a conserved role in inhibiting fat formation. Cell Metab 3:25–34CrossRefPubMedGoogle Scholar
  108. Sun L, Trajkovski M (2014) MiR-27 orchestrates the transcriptional regulation of brown adipogenesis. Metabolism 63:272–282CrossRefPubMedGoogle Scholar
  109. Sun L, Xie H, Mori MA, Alexander R, Yuan B, Hattangadi SM, Liu Q, Kahn CR, Lodish HF (2011) Mir193b-365 is essential for brown fat differentiation. Nat Cell Biol 13:958–965PubMedCentralCrossRefPubMedGoogle Scholar
  110. Tang Q, Chen C, Zhang Y, Dai M, Jiang Y, Wang H, Yu M, Jing W, Tian W (2018) Wnt5a regulates the cell proliferation and adipogenesis via MAPK-independent pathway in early stage of obesity. Cell Biol Int 42:63–74CrossRefPubMedGoogle Scholar
  111. Tarte K, Gaillard J, Lataillade JJ, Fouillard L, Becker M, Mossafa H, Tchirkov A, Rouard H, Henry C, Splingard M, Dulong J, Monnier D, Gourmelon P, Gorin NC, Sensebe L (2010) Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood 115:1549–1553CrossRefGoogle Scholar
  112. Thirumala S, Goebel WS, Woods EJ (2009) Clinical grade adult stem cell banking. Organogenesis 5:143–154PubMedCentralCrossRefPubMedGoogle Scholar
  113. Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 79:1147–1156CrossRefPubMedGoogle Scholar
  114. Trajkovski M, Ahmed K, Esau CC, Stoffel M (2012) MyomiR-133 regulates brown fat differentiation through Prdm16. Nat Cell Biol 14:1330–1335CrossRefPubMedGoogle Scholar
  115. Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000–1004PubMedCentralCrossRefPubMedGoogle Scholar
  116. Unser AM, Tian Y, Xie Y (2015) Opportunities and challenges in three-dimensional brown adipogenesis of stem cells. Biotechnol Adv 33:962–979PubMedCentralCrossRefPubMedGoogle Scholar
  117. Van Zoelen EJ, Duarte I, Hendriks JM, Van Der Woning SP (2016) TGFβ-induced switch from adipogenic to osteogenic differentiation of human mesenchymal stem cells: identification of drug targets for prevention of fat cell differentiation. Stem Cell Res Ther 7:123PubMedCentralCrossRefPubMedGoogle Scholar
  118. Vargas-Castillo A, Fuentes-Romero R, Rodriguez-Lopez LA, Torres N, Tovar AR (2017) Understanding the biology of thermogenic fat: is browning a new approach to the treatment of obesity? Arch Med Res 48:401–413CrossRefPubMedGoogle Scholar
  119. Vellasamy S, Sandrasaigaran P, Vidyadaran S, George E, Ramasamy R (2012) Isolation and characterisation of mesenchymal stem cells derived from human placenta tissue. World J Stem Cells 4:53PubMedCentralCrossRefPubMedGoogle Scholar
  120. Wang QA, Tao C, Gupta RK, Scherer PE (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19:1338PubMedCentralCrossRefPubMedGoogle Scholar
  121. White UA, Tchoukalova YD (2014) Adipose stem cells and Adipogenesis, pp 15–32Google Scholar
  122. Wong JC, Krueger KC, Costa MJ, Aggarwal A, Du H, Mclaughlin TL, Feldman BJ (2016) A glucocorticoid-and diet-responsive pathway toggles adipocyte precursor cell activity in vivo. Sci Signal 9:ra103-ra103Google Scholar
  123. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, Van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–376PubMedCentralCrossRefPubMedGoogle Scholar
  124. Yanovski SZ, Yanovski JA (2014) Long-term drug treatment for obesity: a systematic and clinical review. JAMA 311:74–86PubMedCentralCrossRefPubMedGoogle Scholar
  125. Yao X, Shan S, Zhang Y, Ying H (2011) Recent progress in the study of brown adipose tissue. Cell Biosci 1:35–35PubMedCentralCrossRefPubMedGoogle Scholar
  126. Yarak S, Okamoto OK (2010) Human adipose-derived stem cells: current challenges and clinical perspectives. An Bras Dermatol 85:647–656CrossRefPubMedGoogle Scholar
  127. Yuan Z, Li Q, Luo S, Liu Z, Luo D, Zhang B, Zhang D, Rao P, Xiao J (2016) PPARγ and Wnt signaling in adipogenic and osteogenic differentiation of mesenchymal stem cells. Curr Stem Cell Res Ther 11:216–225CrossRefPubMedGoogle Scholar
  128. Zerradi M, Dereumetz J, Boulet MM, Tchernof A (2014) Androgens, body fat distribution and Adipogenesis. Curr Obes Rep 3:396–403CrossRefPubMedGoogle Scholar
  129. Zhang C, Weng Y, Shi F, Jin W (2016) The Engrailed-1 gene stimulates Brown Adipogenesis. Stem Cells Int 2016:7369491PubMedCentralPubMedGoogle Scholar
  130. Zhao, H., Shang, Q., Pan, Z., Bai, Y., Li, Z., Zhang, H., Zhang, Q., Guo, C., Zhang, L., Wang, Q. (2017) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and Beiging in white adipose tissues. DiabetesGoogle Scholar
  131. Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, Zhang Q, Guo C, Zhang L, Wang Q (2018) Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and Beiging in white adipose tissue. Diabetes 67:235–247CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Moloud Payab
    • 1
  • Parisa Goodarzi
    • 2
  • Najmeh Foroughi Heravani
    • 3
  • Mahdieh Hadavandkhani
    • 3
  • Zeinab Zarei
    • 4
  • Khadijeh Falahzadeh
    • 5
  • Bagher Larijani
    • 6
  • Fakher Rahim
    • 7
  • Babak Arjmand
    • 3
    • 5
  1. 1.Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
  2. 2.Brain and Spinal Cord Injury Research Center, Neuroscience InstituteTehran University of Medical SciencesTehranIran
  3. 3.Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
  4. 4.Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  5. 5.Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences InstituteTehran University of Medical SciencesTehranIran
  6. 6.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences InstituteTehran University of Medical SciencesTehranIran
  7. 7.Health Research Institute, Thalassemia and Hemoglobinopathy Research CenterAhvaz Jundishapur University of Medical SciencesAhvazIran

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