Abstract
Adipose tissue is the major storage sites of energy deposition which can be recruited in times of need to provide fuel for other organs (reviewed in Gunawardana 2014). When normalized to volume, adipose tissue is mainly composed of so-called mature adipocytes which are cells that have the capacity to store energy in the form of triacylglycerols (TAGs) in lipid droplets. When normalized to cell number, only 20–30% of the adipose tissue is made up from mature adipocytes; the other 70–80% are composed of the so-called stromal vascular fraction (SVF), which consists of fibroblasts, adipocyte precursors, endothelial cells, and immune cells (Rosenwald et al. 2013; Wang et al. 2013). This cell heterogeneity clearly demonstrates that adipose tissue is a complex organ with various different functions in the regulation of whole body metabolism. In line with this, over the past several years, our understanding of adipose tissue has changed. Only 20 years ago adipose tissue was considered to be an inert energy storage organ, while nowadays it is accepted that besides its role in energy storage and dissipation, adipose tissue serves as a key organ for the regulation of whole body energy metabolism by cross talk with other organs through the secretion of adipokines, such as tumor necrosis factor α, (TNF-α), interleukin-6 (IL-6), adiponectin, leptin, and resistin, just to mention a few (Bluher and Mantzoros 2015).
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
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–E1253
Bernstein RS, Grant N, Kipnis DM (1975) Hyperinsulinemia and enlarged adipocytes in patients with endogenous hyperlipoproteinemia without obesity or diabetes mellitus. Diabetes 24:207–213
Berry R, Rodeheffer MS (2013) Characterization of the adipocyte cellular lineage in vivo. Nat Cell Biol 15:302–308
Bluher M, Mantzoros CS (2015) From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metab Clin Expl 64:131–145
Cannon B, Hedin A, Nedergaard J (1982) Exclusive occurrence of thermogenin antigen in brown adipose tissue. FEBS Lett 150:129–132
Chau YY, Bandiera R, Serrels A, Martinez-Estrada OM, Qing W, Lee M, Slight J, Thornburn A, Berry R, McHaffie S et al (2014) Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source. Nat Cell Biol 16:367–375
Cinti S (2002) Adipocyte differentiation and transdifferentiation: plasticity of the adipose organ. J Endocrinol Invest 25:823–835
Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ et al (2014) Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156:304–316
Contreras GA, Lee YH, Mottillo EP, Granneman JG (2014) Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation. Am J Physiol Endocrinol Metab 307:E793–799
Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L, Casteilla L (1992) Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 103(Pt 4):931–942
Crossno JT Jr, Majka SM, Grazia T, Gill RG, Klemm DJ (2006) Rosiglitazone promotes development of a novel adipocyte population from bone marrow-derived circulating progenitor cells. J Clin Invest 116:3220–3228
Cypess AML, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360:1509–1517
Dempersmier J, Sambeat A, Gulyaeva O, Paul SM, Hudak CS, Raposo HF, Kwan HY, Kang C, Wong RH, Sul HS (2015) Cold-inducible Zfp516 activates UCP1 transcription to promote browning of white Fat and development of brown Fat. Mol Cell 57:235–246
Desvergne B, Michalik L, Wahli W (2004) Be fit or be sick: peroxisome proliferator-activated receptors are down the road. Mol Endocrinol 18:1321–1332
Elabd C, Chiellini C, Carmona M, Galitzky J, Cochet O, Petersen R, Penicaud L, Kristiansen K, Bouloumie A, Casteilla L et al (2009) Human multipotent adipose-derived stem cells differentiate into functional brown adipocytes. Stem Cells 27:2753–2760
Frontini A, Cinti S (2010) Distribution and development of brown adipocytes in the murine and human adipose organ. Cell Metab 11:253–256
Frontini A, Vitali A, Perugini J, Murano I, Romiti C, Ricquier D, Guerrieri M, Cinti S (2013) White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta 1831:950–959
Gaben-Cogneville AM, Swierczewski E (1979) Studies on cell proliferation in inguinal adipose tissue during early development in the rat. Lipids 14:669–675
Gesta S, Tseng YH, Kahn CR (2007) Developmental origin of fat: tracking obesity to its source. Cell 131:242–256
Green H, Kehinde O (1975) An established pre-adipose cell line and its differentiation in culture. II. Factors affecting adipose conversion. Cell 5:19–27
Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809
Gunawardana SC (2014) Benefits of healthy adipose tissue in the treatment of diabetes. World J Diabetes 5:420–430
Gupta RK, Mepani RJ, Kleiner S, Lo JC, Khandekar MJ, Cohen P, Frontini A, Bhowmick DC, Ye L, Cinti S et al (2012) Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab 15:230–239
He W, Barak Y, Hevener A, Olson P, Liao D, Le J, Nelson M, Ong E, Olefsky JM, Evans RM (2003) Adipose-specific peroxisome proliferator-activated receptor gamma knockout causes insulin resistance in fat and liver but not in muscle. Proc Natl Acad Sci U S A 100:15712–15717
Himms-Hagen J, Melnyk A, Zingaretti MC, Ceresi E, Barbatelli G, Cinti S (2000) Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am J Physiol Cell Physiol 279:C670–C681
Hirsch J, Batchelor B (1976) Adipose tissue cellularity in human obesity. Clin Endocrinol Metab 5:299–311
Hubbard RW, Matthew WT (1971) Growth and lipolysis of rat adipose tissue: effect of age, body weight, and food intake. J Lipid Res 12:286–293
Hudak CS, Gulyaeva O, Wang Y, Park SM, Lee L, Kang C, Sul HS (2014) Pref-1 marks very early mesenchymal precursors required for adipose tissue development and expansion. Cell Rep 8:678–687
Kaplan ML, Trout JR, Leveille GA (1976) Adipocyte size distribution in ob/ob mice during preobese and obese phases of development. Proc Soc Exp Biol Med 153:476–482
Kwan HY, Chao X, Su T, Fu X, Liu B, Tse AK, Fong WF, Yu Z (2014) Dietary lipids and adipocytes: potential therapeutic targets in cancers. J Nutr Biochem 26:303–311
Lee YH, Petkova AP, Mottillo EP, Granneman JG (2012) In vivo identification of bipotential adipocyte progenitors recruited by beta3-adrenoceptor activation and high-fat feeding. Cell Metab 15:480–491
Lee YH, Petkova AP, Konkar AA, Granneman JG (2015) Cellular origins of cold-induced brown adipocytes in adult mice. FASEB J 29:286–299
Lemonnier D (1972) Effect of age, sex, and sites on the cellularity of the adipose tissue in mice and rats rendered obese by a high-fat diet. J Clin Invest 51:2907–2915
Leonhardt W, Hanefeld M, Schneider H, Haller H (1972) Human adipocyte volumes: maximum size, and correlation to weight index in maturity onset-diabetes. Diabetologia 8:287–291
Leonhardt W, Haller H, Hanefeld M (1978) The adipocyte volume in human adipose tissue: II. Observations in diabetes mellitus, primary hyperlipoproteinemia and weight reduction. Int J Obes (Lond) 2:429–439
Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM et al (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119:121–135
Linhart HG, Ishimura-Oka K, DeMayo F, Kibe T, Repka D, Poindexter B, Bick RJ, Darlington GJ (2001) C/EBPalpha is required for differentiation of white, but not brown, adipose tissue. Proc Natl Acad Sci U S A 98:12532–12537
Long JZ, Svensson KJ, Tsai L, Zeng X, Roh HC, Kong X, Rao RR, Lou J, Lokurkar I, Baur W et al (2014) A smooth muscle-like origin for beige adipocytes. Cell Metab 19:810–820
Meissburger B, Ukropec J, Roeder E, Beaton N, Geiger M, Teupser D, Civan B, Langhans W, Nawroth PP, Gasperikova D et al (2011) Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma. EMBO Mol Med 3:637–651
Napolitano L (1963) The differentiation of white adipose cells. An electron microscope study. J Cell Biol 18:663–679
Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J (2010) Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285:7153–7164
Poissonnet CM, Burdi AR, Bookstein FL (1983) Growth and development of human adipose tissue during early gestation. Early Hum Dev 8:1–11
Rodeheffer MS, Birsoy K, Friedman JM (2008) Identification of white adipocyte progenitor cells in vivo. Cell 135:240–249
Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7:885–896
Rosenwald M, Perdikari A, Rulicke T, Wolfrum C (2013) Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 15:659–667
Sanchez-Gurmaches J, Guertin DA (2014a) Adipocyte lineages: tracing back the origins of fat. Biochim Biophys Acta 1842:340–351
Sanchez-Gurmaches J, Guertin DA (2014b) Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat Commun 5:4099
Sanchez-Gurmaches J, Hung CM, Sparks CA, Tang Y, Li H, Guertin DA (2012) PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab 16:348–362
Schulz TJ, Huang TL, Tran TT, Zhang H, Townsend KL, Shadrach JL, Cerletti M, McDougall LE, Giorgadze N, Tchkonia T et al (2011) Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. Proc Natl Acad Sci U S A 108:143–148
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 6:38–54
Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, Cohen P, Cinti S, Spiegelman BM (2011) Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 121:96–105
Sera Y, LaRue AC, Moussa O, Mehrotra M, Duncan JD, Williams CR, Nishimoto E, Schulte BA, Watson PM, Watson DK et al (2009) Hematopoietic stem cell origin of adipocytes. Exp Hematol 37: 1108–1120, 1120 e1101-1104
Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T et al (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787
Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, Tallquist MD, Graff JM (2008) White fat progenitor cells reside in the adipose vasculature. Science 322:583–586
Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K et al (2007) Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci U S A 104:4401–4406
Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A, Smorlesi A, Perugini J, De Matteis R, Sbarbati A et al (2012) The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab 15:222–229
Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y et al (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000–1004
Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM (2006) Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab 3:333–341
Vegiopoulos A, Muller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E, Ostertag A, Berriel Diaz M, Rozman J, Hrabe de Angelis M, Nusing RM et al (2010) Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328:1158–1161
Virtanen KNL, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360:1518–1525
Vitali A, Murano I, Zingaretti MC, Frontini A, Ricquier D, Cinti S (2012) The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res 53:619–629
Wang QA, Tao C, Gupta RK, Scherer PE (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19:1338–1344
Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G et al (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–376
Young P, Wilson S, Arch JR (1984) Prolonged beta-adrenoceptor stimulation increases the amount of GDP-binding protein in brown adipose tissue mitochondria. Life Sci 34(12):1111–1117
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Müller, S., Kulenkampff, E., Wolfrum, C. (2015). Adipose Tissue Stem Cells. In: Herzig, S. (eds) Metabolic Control. Handbook of Experimental Pharmacology, vol 233. Springer, Cham. https://doi.org/10.1007/164_2015_13
Download citation
DOI: https://doi.org/10.1007/164_2015_13
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-29804-7
Online ISBN: 978-3-319-29806-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)