Abstract
Adipose tissue growth occurs in the body at specific sites called adipose tissue depots. These fats depots form from the accumulation of adipocytes, the predominant cells of adipose tissue that are filled with triglycerides. Lately, adipose tissue is considered much more than an energy storage site. It is a source of hormones, growth factors, cytokines, and signaling molecules that regulate body metabolism. Furthermore, adipose tissue growth occurs through increases in size and number of adipocytes, which in turn is determined by a balance of lipolysis, lipogenesis, and adipocyte proliferation. Recently, a life cycle for adipocytes is acknowledged, which includes proliferation, growth arrest, clonal expansion, terminal differentiation, and apoptosis. Several factors affect adipocytes in their life cycle, and in the current chapter, major factors that influence the adipocyte life cycle are categorized into adipokines, transcription factors, hormonal factors, and nutritional and environmental factors. Studying these factors that influence and target different stages of the adipocyte life cycle might prove beneficial in understanding the physiological and pathophysiological mechanisms underlying adipose tissue development.
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
Accili D, Taylor SI (1991) Targeted inactivation of the insulin receptor gene in mouse 3T3-L1 fibroblasts via homologous recombination. Proc Natl Acad Sci USA 88(11):4708–4712
Ahima RS, Flier JS (2000) Adipose tissue as an endocrine organ. Trends Endocrinol Metab 11(8):327–332
Ambati S, Kim HK et al (2007) Effects of leptin on apoptosis and adipogenesis in 3T3-L1 adipocytes. Biochem Pharmacol 73(3):378–384
Baile CA, Della-Fera MA et al (2000) Regulation of metabolism and body fat mass by leptin. Annu Rev Nutr 20:105–127
Banerjee RR, Lazar MA (2003) Resistin: molecular history and prognosis. J Mol Med 81(4):218–226
Barak Y, Nelson MC et al (1999) PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 4(4):585–595
Beltowski J (2006) Apelin and visfatin: unique “beneficial” adipokines upregulated in obesity? Med Sci Monit 12(6):RA112–RA119
Bjorntorp P (1991) Metabolic implications of body fat distribution. Diabetes Care 14(12):1132–1143
Bonet ML, Ribot J et al (2003) Vitamin A and the regulation of fat reserves. Cell Mol Life Sci 60(7):1311–1321
Braissant O, Foufelle F et al (1996) Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 137(1):354–366
Brotons JA, Olea-Serrano MF et al (1995) Xenoestrogens released from lacquer coatings in food cans. Environ Health Perspect 103(6):608–612
Brun RP, Spiegelman BM (1997) PPAR gamma and the molecular control of adipogenesis. J Endocrinol 155(2):217–218
Brun RP, Tontonoz P et al (1996) Differential activation of adipogenesis by multiple PPAR isoforms. Genes Dev 10(8):974–984
Buckley JD, Howe PR (2009) Anti-obesity effects of long-chain omega-3 polyunsaturated fatty acids. Obes Rev 10(6):648–659
Cadigan KM, Nusse R (1997) Wnt signaling: a common theme in animal development. Genes Dev 11(24):3286–3305
Campion J, Milagro FI et al (2006) Differential gene expression and adiposity reduction induced by ascorbic acid supplementation in a cafeteria model of obesity. J Physiol Biochem 62(2):71–80
Chandran M, Phillips SA et al (2003) Adiponectin: more than just another fat cell hormone? Diabetes Care 26(8):2442–2450
Cheng S, Massaro JM et al (2010) Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes 59(1):242–248
Dang ZC (2009) Dose-dependent effects of soy phyto-oestrogen genistein on adipocytes: mechanisms of action. Obes Rev 10(3):342–349
Della-Fera MA, Qian H et al (2001) Adipocyte apoptosis in the regulation of body fat mass by leptin. Diabetes Obes Metab 3(5):299–310
Dieudonne MN, Pecquery R et al (2000) Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes: evidence for sex and site-related specificities and possible involvement of insulin-like growth factor 1 receptor and peroxisome proliferator-activated receptor gamma2. Endocrinology 141(2):649–656
Duncan RE, Ahmadian M et al (2007) Regulation of lipolysis in adipocytes. Annu Rev Nutr 27:79–101
Ejaz A, Wu D et al (2009) Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr 139(5):919–925
Entenmann G, Hauner H (1996) Relationship between replication and differentiation in cultured human adipocyte precursor cells. Am J Physiol 270(4 Pt 1):C1011–C1016
Etherton TD (2000) The biology of somatotropin in adipose tissue growth and nutrient partitioning. J Nutr 130(11):2623–2625
Fain JN, Madan AK et al (2004) Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 145(5):2273–2282
Fernandez-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24(3):278–301
Fernyhough ME, Okine E et al (2007) PPARgamma and GLUT-4 expression as developmental regulators/markers for preadipocyte differentiation into an adipocyte. Domest Anim Endocrinol 33(4):367–378
Forman BM, Tontonoz P et al (1995) 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83(5):803–812
Frayn KN, Karpe F et al (2003) Integrative physiology of human adipose tissue. Int J Obes Relat Metab Disord 27(8):875–888
Fruebis J, Tsao TS et al (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98(4):2005–2010
Fruhbeck G, Becerril S et al (2009) BAT: a new target for human obesity? Trends Pharmacol Sci 30(8):387–396
Fu Y, Luo N et al (2005) Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res 46(7):1369–1379
Fukuhara A, Matsuda M et al (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307(5708):426–430
Garrett IR, Gutierrez G et al (2001) Statins and bone formation. Curr Pharm Des 7(8):715–736
Girard J (1994) Insulin resistance: role in type 2 diabetes. Diabetes Metab 20(3 Pt 2):330–336
Goodpaster BH, Thaete FL et al (1997) Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes 46(10):1579–1585
Green H, Kehinde O (1979) Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line. J Cell Physiol 101(1):169–171
Greenberg AS, Nordan RP et al (1992) Interleukin 6 reduces lipoprotein lipase activity in adipose tissue of mice in vivo and in 3T3-L1 adipocytes: a possible role for interleukin 6 in cancer cachexia. Cancer Res 52(15):4113–4116
Gregoire FM (2001) Adipocyte differentiation: from fibroblast to endocrine cell. Exp Biol Med (Maywood) 226(11):997–1002
Gregoire FM, Smas CM et al (1998) Understanding adipocyte differentiation. Physiol Rev 78(3):783–809
Guo X, Liao K (2000) Analysis of gene expression profile during 3T3-L1 preadipocyte differentiation. Gene 251(1):45–53
Hacker G (2000) The morphology of apoptosis. Cell Tissue Res 301(1):5–17
Halaas JL, Gajiwala KS et al (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269(5223):543–546
Hartman HB, Hu X et al (2002) Mechanisms regulating adipocyte expression of resistin. J Biol Chem 277(22):19754–19761
Hotta K, Funahashi T et al (2001) Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50(5):1126–1133
Igney FH, Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2(4):277–288
Inadera H, Shimomura A (2005) Environmental chemical tributyltin augments adipocyte differentiation. Toxicol Lett 159(3):226–234
Joza N, Susin SA et al (2001) Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 410(6828):549–554
Justesen J, Stenderup K et al (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2(3):165–171
Karastergiou K, Mohamed-Ali V (2010) The autocrine and paracrine roles of adipokines. Mol Cell Endocrinol 318(1–2):69–78
Kawai M, Namba N et al (2007) Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARgamma pathway. J Mol Endocrinol 38(1–2):19–34
Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89(6):2548–2556
Kidani T, Kamei S et al (2010) Bisphenol A downregulates Akt signaling and inhibits adiponectin production and secretion in 3T3-L1 adipocytes. J Atheroscler Thromb 17(8):834–843
Kim JB, Wright HM et al (1998) ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci USA 95(8):4333–4337
Kim HK, Nelson-Dooley C et al (2006) Genistein decreases food intake, body weight, and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. J Nutr 136(2):409–414
Kirkland JL, Tchkonia T et al (2002) Adipogenesis and aging: does aging make fat go MAD? Exp Gerontol 37(6):757–767
Kloting N, Koch L et al (2008) Autocrine IGF-1 action in adipocytes controls systemic IGF-1 concentrations and growth. Diabetes 57(8):2074–2082
Kong J, Li YC (2006) Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells. Am J Physiol Endocrinol Metab 290(5):E916–E924
Konieczny SF, Emerson CP Jr (1984) 5-Azacytidine induction of stable mesodermal stem cell lineages from 10T1/2 cells: evidence for regulatory genes controlling determination. Cell 38(3):791–800
Lagouge M, Argmann C et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127(6):1109–1122
Lane MD, Flores-Riveros JR et al (1990) Insulin-receptor tyrosine kinase and glucose transport. Diabetes Care 13(6):565–575
Lane MD, Tang QQ et al (1999) Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem Biophys Res Commun 266(3):677–683
Large V, Reynisdottir S et al (1999) Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. J Lipid Res 40(11):2059–2066
Lefterova MI, Lazar MA (2009) New developments in adipogenesis. Trends Endocrinol Metab 20(3):107–114
Levacher C, Sztalryd C et al (1984) Effects of thyroid hormones on adipose tissue development in Sherman and Zucker rats. Am J Physiol 246(1 Pt 1):C50–C56
Li Y, Wang C et al (2010) Effects of multivitamin and mineral supplementation on adiposity, energy expenditure and lipid profiles in obese Chinese women. Int J Obes (Lond) 34(6):1070–1077
Lin J, Della-Fera MA et al (2005) Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes. Obes Res 13(6):982–990
Locksley RM, Killeen N et al (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104(4):487–501
Loskutoff DJ, Samad F (1998) The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 18(1):1–6
Lupattelli G, Scarponi AM et al (2004) Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women. Metabolism 53(6):744–748
Madsen L, Petersen RK et al (2005) Regulation of adipocyte differentiation and function by polyunsaturated fatty acids. Biochim Biophys Acta 1740(2):266–286
Maeda N, Shimomura I et al (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8(7):731–737
Margetic S, Gazzola C et al (2002) Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 26(11):1407–1433
Maurin AC, Chavassieux PM et al (2000) Influence of mature adipocytes on osteoblast proliferation in human primary cocultures. Bone 26(5):485–489
Meseguer A, Puche C et al (2002) Sex steroid biosynthesis in white adipose tissue. Horm Metab Res 34(11–12):731–736
Miller JR, Hocking AM et al (1999) Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways. Oncogene 18(55):7860–7872
Moldes M, Zuo Y et al (2003) Peroxisome-proliferator-activated receptor gamma suppresses Wnt/beta-catenin signalling during adipogenesis. Biochem J 376(Pt 3):607–613
Mori T, Sakaue H et al (2005) Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J Biol Chem 280(13):12867–12875
Morrison RF, Farmer SR (2000) Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 130(12):3116S–3121S
Murano I, Barbatelli G et al (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49(7):1562–1568
Ognjanovic S, Bao S et al (2001) Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes. J Mol Endocrinol 26(2):107–117
Oxlund H, Andreassen TT (2004) Simvastatin treatment partially prevents ovariectomy-induced bone loss while increasing cortical bone formation. Bone 34(4):609–618
Pang C, Gao Z et al (2008) Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity. Am J Physiol Endocrinol Metab 295(2):E313–E322
Park HJ, Yang JY et al (2008) Combined effects of genistein, quercetin, and resveratrol in human and 3T3-L1 adipocytes. J Med Food 11(4):773–783
Park HJ, Della-Fera MA et al (2009) Genistein inhibits differentiation of primary human adipocytes. J Nutr Biochem 20(2):140–148
Pessin JE, Thurmond DC et al (1999) Molecular basis of insulin-stimulated GLUT4 vesicle trafficking. Location! Location! Location! J Biol Chem 274(5):2593–2596
Poissonnet CM, Burdi AR et al (1983) Growth and development of human adipose tissue during early gestation. Early Hum Dev 8(1):1–11
Prins JB, O’Rahilly S (1997) Regulation of adipose cell number in man. Clin Sci (Lond) 92(1):3–11
Qi Q, Wang J et al (2008) Associations of resistin with inflammatory and fibrinolytic markers, insulin resistance, and metabolic syndrome in middle-aged and older Chinese. Eur J Endocrinol 159(5):585–593
Qian H, Azain MJ et al (1998) Brain administration of leptin causes deletion of adipocytes by apoptosis. Endocrinology 139(2):791–794
Rayalam S, Della-Fera MA et al (2008a) Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem 19(11):717–726
Rayalam S, Yang JY et al (2008b) Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res 22(10):1367–1371
Rayalam S, Yang JY et al (2009) Anti-obesity effects of xanthohumol plus guggulsterone in 3T3-L1 adipocytes. J Med Food 12(4):846–853
Rosen ED, Spiegelman BM (2000) Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol 16:145–171
Ross SE, Hemati N et al (2000) Inhibition of adipogenesis by Wnt signaling. Science 289(5481):950–953
Ruan H, Lodish HF (2003) Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. Cytokine Growth Factor Rev 14(5):447–455
Ruan H, Miles PDG et al (2002) Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha – implications for insulin resistance. Diabetes 51(11):3176–3188
Ryan AS, Nicklas BJ (1999) Age-related changes in fat deposition in mid-thigh muscle in women: relationships with metabolic cardiovascular disease risk factors. Int J Obes Relat Metab Disord 23(2):126–132
Sadowski HB, Wheeler TT et al (1992) Gene expression during 3T3-L1 adipocyte differentiation. Characterization of initial responses to the inducing agents and changes during commitment to differentiation. J Biol Chem 267(7):4722–4731
Sargis RM, Johnson DN et al (2010) Environmental endocrine disruptors promote adipogenesis in the 3T3-L1 cell line through glucocorticoid receptor activation. Obesity (Silver Spring) 18(7):1283–1288
Sasaki S, Kawai K et al (2006) Thyroid hormones and lipid metabolism. Nippon Rinsho 64(12):2323–2329
Schmid B, Rippmann JF et al (2005) Inhibition of fatty acid synthase prevents preadipocyte differentiation. Biochem Biophys Res Commun 328(4):1073–1082
Sethi JK, Vidal-Puig A (2005) Visfatin: the missing link between intra-abdominal obesity and diabetes? Trends Mol Med 11(8):344–347
Shen WJ, Sridhar K et al (1999) Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein. Proc Natl Acad Sci USA 96(10):5528–5532
Slavin BG (1979) Fine structural studies on white adipocyte differentiation. Anat Rec 195(1):63–72
Smas CM, Chen L et al (1999) Transcriptional repression of pref-1 by glucocorticoids promotes 3T3-L1 adipocyte differentiation. J Biol Chem 274(18):12632–12641
Smith SR, Lovejoy JC et al (2001) Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism 50(4):425–435
Smith J, Al-Amri M et al (2006) The adipocyte life cycle hypothesis. Clin Sci (Lond) 110(1):1–9
Snijder MB, Dekker JM et al (2004) Trunk fat and leg fat have independent and opposite associations with fasting and postload glucose levels: the Hoorn study. Diabetes Care 27(2):372–377
Spiegelman BM, Frank M et al (1983) Molecular cloning of mRNA from 3T3 adipocytes. Regulation of mRNA content for glycerophosphate dehydrogenase and other differentiation-dependent proteins during adipocyte development. J Biol Chem 258(16):10083–10089
Spiegelman BM, Choy L et al (1993) Regulation of adipocyte gene expression in differentiation and syndromes of obesity/diabetes. J Biol Chem 268(10):6823–6826
Stewart PM, Tomlinson JW (2002) Cortisol, 11 beta-hydroxysteroid dehydrogenase type 1 and central obesity. Trends Endocrinol Metab 13(3):94–96
Storch J, Thumser AE (2000) The fatty acid transport function of fatty acid-binding proteins. Biochim Biophys Acta 1486(1):28–44
Stunkard AJ, Sorensen TI et al (1986) An adoption study of human obesity. N Engl J Med 314(4):193–198
Takeuchi T, Tsutsumi O et al (2004) Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocr J 51(2):165–169
Teglund S, McKay C et al (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93(5):841–850
Umek RM, Friedman AD et al (1991) CCAAT-enhancer binding protein: a component of a differentiation switch. Science 251(4991):288–292
Viroonudomphol D, Pongpaew P et al (2003) The relationships between anthropometric measurements, serum vitamin A and E concentrations and lipid profiles in overweight and obese subjects. Asia Pac J Clin Nutr 12(1):73–79
Viswakarma N, Jia Y et al (2010) Coactivators in PPAR-regulated gene expression. PPAR Res 2010:250126
Walker BR, Connacher AA et al (1995) Carbenoxolone increases hepatic insulin sensitivity in man: a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J Clin Endocrinol Metab 80(11):3155–3159
Wallenius V, Wallenius K et al (2002) Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8(1):75–79
Wang H, Eckel RH (2009) Lipoprotein lipase: from gene to obesity. Am J Physiol Endocrinol Metab 297(2):E271–E288
Wang YW, Jones PJ (2004) Conjugated linoleic acid and obesity control: efficacy and mechanisms. Int J Obes Relat Metab Disord 28(8):941–955
Wang B, Jenkins JR et al (2005) Expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture: integrated response to TNF-alpha. Am J Physiol Endocrinol Metab 288(4):E731–E740
Wang Y, Kim KA et al (2006) Pref-1, a preadipocyte secreted factor that inhibits adipogenesis. J Nutr 136(12):2953–2956
White UA, Stephens JM (2010) Transcriptional factors that promote formation of white adipose tissue. Mol Cell Endocrinol 318(1–2):10–14
Xing H, Northrop JP et al (1997) TNF alpha-mediated inhibition and reversal of adipocyte differentiation is accompanied by suppressed expression of PPARgamma without effects on Pref-1 expression. Endocrinology 138(7):2776–2783
Yang JY, Della-Fera MA et al (2007) Effect of xanthohumol and isoxanthohumol on 3T3-L1 cell apoptosis and adipogenesis. Apoptosis 12(11):1953–1963
Yang JY, Della-Fera MA et al (2008) Guggulsterone inhibits adipocyte differentiation and induces apoptosis in 3T3-L1 cells. Obesity (Silver Spring) 16(1):16–22
Yu YH, Zhang Y et al (2002) Posttranscriptional control of the expression and function of diacylglycerol acyltransferase-1 in mouse adipocytes. J Biol Chem 277(52):50876–50884
Yuen BS, Owens PC et al (2003) Leptin alters the structural and functional characteristics of adipose tissue before birth. FASEB J 17(9):1102–1104
Zuo Z, Chen S et al (2011) Tributyltin causes obesity and hepatic steatosis in male mice. Environ Toxicol 26(1):79–85
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Rayalam, S., Baile, C.A. (2012). Adipocyte Growth and Factors Influencing Adipocyte Life Cycle. In: Symonds, M. (eds) Adipose Tissue Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0965-6_7
Download citation
DOI: https://doi.org/10.1007/978-1-4614-0965-6_7
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-0964-9
Online ISBN: 978-1-4614-0965-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)