Abstract
Our understanding of adipose tissue physiology and pathophysiology has substantially increased during the last decade. Notably, white adipose tissue (WAT) dysfunction has been proposed as a key determinant of obesity-associated metabolic complications. WAT is a complex metabolic organ composed of many cell types, including adipocytes as the main cell type involved in energy storage. Adipocytes also synthesize numerous molecules involved in the regulation of energy balance, vascular homeostasis, and insulin sensitivity. In obesity, WAT expansion is associated with intensified structural remodeling that compromises the tissue’s metabolic and secretory functions. Failure to efficiently store lipids in WAT results in a “spillover” of the excess of lipids into non-adipose tissues, which further disrupts metabolic homeostasis and contributes to the development of obesity-related pathologies, known collectively as metabolic syndrome. In contrast, brown adipose tissue (BAT) is an energy-dissipating thermogenic organ that produces heat by uncoupling mitochondrial fatty acid oxidation. Activation of BAT thermogenesis can ameliorate the effects of WAT dysfunction in metabolically compromised mouse models. The recent rediscovery of BAT in humans has raised the possibility that BAT could be a therapeutic target for metabolic syndrome. In this chapter, we will discuss important structural and cellular features of the WAT and BAT and how obesity alters WAT and BAT structure and function.
References
Agarwal, AK, Garg, A Genetic disorders of adipose tissue development, differentiation, and death. Annu Rev Genomics Hum Genet. 2006; 7: 175–99.
Andreozzi, F, Laratta, E, Procopio, C, et al. Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. Mol Cell Biol. 2007; 27: 2372–83.
Arbeeny, CM, Meyers, DS, Hillyer, DE, et al. Metabolic alterations associated with the antidiabetic effect of beta 3-adrenergic receptor agonists in obese mice. Am J Physiol Endocrinol Metab. 1995; 268: E678–E684.
Bagchi, M, Kim, LA, Boucher, J, et al. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance. FASEB J. 2013; 27: 3257–71.
Bartelt, A, Bruns, OT, Reimer, R, et al. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011; 17: 200–5.
Berry, DC, Stenesen, D, Zeve, D, et al. The developmental origins of adipose tissue. Development. 2013; 140: 3939–49.
Bjørndal, B, Burri, L, Staalesen, V, et al. Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. J Obes. 2011; 490650.
Bordicchia, M, Liu, D, Amri, E, et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012; 122: 1022–36.
Borén, J, Taskinen, M-R, Olofsson, S-O, et al. Ectopic lipid storage and insulin resistance: a harmful relationship. J Intern Med. 2013; 274: 25–40.
Boström, P, Wu, J, Jedrychowski, MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481: 463–8.
Bourlier, V, Zakaroff-Girard, A, Miranville, A, et al. Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation. 2008; 117: 806–15.
Bråkenhielm, E, Veitonmäki, N, Cao, R, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci USA. 2004; 101: 2476–81.
Brito, NA, Brito, MN, Bartness, TJ Differential sympathetic drive to adipose tissues after food deprivation, cold exposure or glucoprivation. Am J Physiol Regul Integr Comp Physiol. 2008; 294: R1445–R1452.
Cancello, R, Tordjman, J, Poitou, C, et al. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes. 2006; 55: 1554–61.
Cannon, B, Nedergaard, J Brown Adipose Tissue: function and physiological significance. Physiol Rev. 2004; 84: 277–359.
Cannon, B, Nedergaard, J Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Expl Biol. 2011; 214: 242–53.
Cao, R, Brakenhielm, E, Wahlestedt, C, et al. Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. PNAS. 2001; 98: 6390–5.
Carobbio, S, Rosen, B, Vidal-Puig, A Adipogenesis: new insights into brown adipose tissue differentiation. J Mol Endocrinol. 2013; 51: T75–T85.
Carrière, A, Jeanson, Y, Berger-Müller, S, et al. Browning of white adipose cells by intermediate metabolites: an adaptive mechanism to alleviate redox pressure. Diabetes. 2014; 63: 3253–65.
Chen, H, Montagnani, M, Funahashi, T, et al. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem. 2003; 278: 45021–6.
Cinti, S, Mitchell, G, Barbatelli, G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005; 46: 2347–55.
Clemente-Postigo, M, Queipo-Ortuño, MI, Fernandez-Garcia, D, et al. Adipose tissue gene expression of factors related to lipid processing in obesity. PLoS One. 2011; 6: e24783.
Collins, S, Daniel, KW, Rohlfs, EM, et al. Impaired expression and functional activity of the beta 3- and beta 1-adrenergic receptors in adipose tissue of congenitally obese (C57BL/6J ob/ob) mice. Mol Endocrinol. 1994; 8: 518–27.
Coppack, SW Pro-inflammatory cytokines and adipose tissue. PNAS. 2001; 60: 349–56.
Craft, CS, Pietka, TA, Schappe, T, et al. The extracellular matrix protein MAGP1 supports thermogenesis and protects against obesity and diabetes through regulation of TGF-β. Diabetes. 2014; 63: 1920–32.
Cypess, AM, Lehman, S, Williams, G, et al. Identification and importance of brown adipose tissue in adult humans. New Eng J Med. 2009; 360: 1509–17.
Dani, C Activins in adipogenesis and obesity. Int J Obes (Lond). 2013; 37: 163–6.
Divoux, A, Moutel, S, Poitou, C, et al. Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes. J Clin Endocrinol Metab. 2012; 97: E1677–E1685.
Divoux, A, Tordjman, J, Lacasa, D, et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes. 2010; 59: 2817–25.
Dreier, R, Grässel, S, Fuchs, S, et al. Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Exp Cell Res. 2004; 297: 303–12.
Duffaut, C, Galitzky, J, Lafontan, M, et al. Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun. 2009; 384: 482–425.
Elias, I, Franckhauser, S, Bosch, F New insights into adipose tissue VEGF-A actions in the control of obesity and insulin resistance. Adipocyte. 2013; 2: 109–12.
Fain, JN Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006; 74: 443–77.
Feldmann, HM, Golozoubova, V, Cannon, B, et al. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009; 9: 203–9.
Fernandez, JA, Mampel, T, Villarroya, F, et al. Direct assessment of brown adipose tissue as a site of systemic tri-iodothyronine production in the rat. Biochem J. 1987; 243: 281–4.
Fisher, FM, Kleiner, S, Douris, N, et al. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Gene Dev. 2012; 26: 271–81.
Frontini, A, Vitali, A, Perugini, J, et al. White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochem Biophys Acta. 2013; 1831: 950–9.
Gealekman, O, Guseva, N, Hartigan, C, et al. Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity. Circulation. 2011; 123: 186–94.
Gilsanz, V, Smith, M, Goodarzian, F, et al. Changes in brown adipose tissue in boys and girls during childhood and puberty. J Pediatr. 2013; 160: 604–9.
Giordano, A, Coppari, R, Castellucci, M, et al. Sema3a is produced by brown adipocytes and its secretion is reduced following cold acclimation. J Neurocytol. 2001; 30: 5–10.
Giordano, A, Morroni, M, Santone, G, et al. Tyrosine hydroxylase, neuropeptide Y, substance P, calcitonin gene-related peptide and vasoactive intestinal peptide in nerves of rat periovarian adipose tissue: an immunohistochemical and ultrastructural investigation. J Neurocytol. 1996; 25: 125–36.
Giorgino, F, Laviola, L, Eriksson, JW Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies. Acta Physiol Scand. 2005; 183: 13–30.
Gnad, T, Scheibler, S, von Kügelgen, I, et al. Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors. Nature. 2014; [Epub ahead of print].
Hansen, JB, Kristiansen, K Regulatory circuits controlling white versus brown adipocyte differentiation. Biochem J. 2006; 398: 153–68.
Haraida, S, Nerlich, AG, Wiest, I, et al. Distribution of basement membrane components in normal adipose tissue and in benign and malignant tumors of lipomatous origin. Mod Pathol. 1996; 9: 137–44.
Henegar, C, Tordjman, J, Achard, V, et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol. 2008; 9: R14.
Himms-Hagen, J, Cui, J, Danforth, E, et al. Effect of CL-316,243, a thermogenic beta 3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol-Reg I. 1994; 266: R1371–R1382.
Hocking, SL, Wu, LE, Guilhaus, M, et al. Intrinsic depot-specific differences in the secretome of adipose tissue, preadipocytes, and adipose tissue-derived microvascular endothelial cells. Diabetes. 2010; 59: 3008–16.
Hondares, E, Gallego-Escuredo, JM, Flachs, P, et al. Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue. Metabolism. 2014; 63: 312–7.
Hondares, E, Iglesias, R, Giralt, A, et al. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem. 2011a; 286: 12983–90.
Hondares, E, Rosell, M, Gonzalez, F, et al. Hepatic FGF21 expression is induced at birth via PPARa in response to milk intake and contributes to thermogenic activation of neonatal brown fat. Cell Metab. 2011b; 11: 206–12.
Hu, P, Luo, B-H Integrin bi-directional signaling across the plasma membrane. J Cell Physiol. 2013; 228: 306–12.
Imhof, BA, Aurrand-Lions, M Angiogenesis and inflammation face off. Nat Med. 2006; 12: 171–2.
Isakson, P, Hammarstedt, A, Gustafson, B, et al. Impaired preadipocyte differentiation in human abdominal obesity: role of Wnt, tumor necrosis factor-alpha, and inflammation. Diabetes. 2009; 58: 1550–7.
Janssen, I, Powell, LH, Kazlauskaite, R, et al. Testosterone and visceral fat in midlife women: the Study of Women’s Health Across the Nation (SWAN) fat patterning study. Obes (Silver Spring). 2010; 18: 604–10.
Keophiphath, M, Achard, V, Henegar, C, et al. Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol. 2009; 23: 11–24.
Kim, C-S, Park, H-S, Kawada, T, et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes. 2006; 30: 1347–55.
Kintscher, U, Hartge, M, Hess, K, et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Aterioscler Thromb Vasc Biol. 2008; 28: 1304–10.
Kobashi, C, Urakaze, M, Kishida, M, et al. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res. 2005; 97: 1245–52.
Kobayashi, H, Ouchi, N, Kihara, S, et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res. 2004; 94: e27–e31.
Kreier, F, Buijs, RM Evidence for parasympathetic innervation of white adipose tissue, clearing up some vagaries. Am J Physiol regul Integr Comp Physiol. 2007; 293: R548–9; author reply R550–2, discussion R553–4.
Kunduzova, O, Alet, N, Delesque-Touchard, N, et al. Apelin/APJ signaling system: a potential link between adipose tissue and endothelial angiogenic processes. FASEB J. 2008; 22: 4146–53.
Kwon, E-Y, Shin, S-K, Cho, Y-Y, et al. Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity. BMC Genomics. 2012; 13: 450.
Lafontan, M, Langin, D Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res. 2009; 48: 275–97.
Van der Lans, AAJJ, Hoeks, J, Brans, B, et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest. 2013; 123: 3395–403.
Lean, M Brown adipose tissue in humans. Proc Nutr Soc. 1989; 48: 243–56.
LeBleu, VS, Macdonald, B, Kalluri, R Structure and function of basement membranes. Exp Biol Med. 2007; 232: 1121–9.
Lee, P, Greenfield, JR, Ho, KKY, et al. A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol-Endoc M. 2010; 299: E601–606.
Lee, P, Linderman, JD, Smith, S, et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014a; 19: 302–9.
Lee, P, Smith, S, Linderman, J, et al. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes. 2014b; 63: 3686–98.
Lee, Y-H, Petkova, AP, Mottillo, EP, et al. In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high-fat feeding. Cell Metab. 2012; 15: 480–91.
Li, G, Klein, RL, Matheny, M, et al. Induction of uncoupling protein 1 by central interleukin-6 gene delivery is dependent on sympathetic innervation of brown adipose tissue and underlies one mechanism of body weight reduction in rats. Neuroscience. 2002; 115: 879–89.
Lichtenbelt, WDVM, Vanhommerig, JW, Smulders, NM, et al. Cold-activated brown adipose tissue in healthy men. New Eng J Med. 2009; 360: 1500–8.
Lidell, ME, Betz, MJ, Leinhard, OD, et al. Evidence for two types of brown adipose tissue in humans. Nat Med. 2013; 19: 631–4.
Lidell, ME, Seifert, EL, Westergren, R, et al. The adipocyte-expressed forkhead transcription factor Foxc2 regulates metabolism through altered mitochondrial function. Diabetes. 2011; 60: 427–35.
Liu, X, Pérusse, F, Bukowiecki, LJ Mechanisms of the antidiabetic effects of the β3-adrenergic agonist CL-316243 in obese Zucker-ZDF rats. Am J Physiol Regul Integr Comp Physiol. 1998; 274: R1212–R1219.
López, M, Alvarez, C V, Nogueiras, R, et al. Energy balance regulation by thyroid hormones at central level. Trends Mol Med. 2013; 19: 418–27.
Love-Gregory, L, Abumrad, NA CD36 genetics and the metabolic complications of obesity. Curr Opin Clin Nutr Metab Care. 2011; 14: 527–34.
Lowell, BB, S-Susulic, V, Hamann, A, et al. Development of obesity in transgenic mice after genetic ablation of adipose tissue. Nature. 1993; 366: 740–2.
Lumeng, CN, Bodzin, JL, Saltiel, AR Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007a; 117: 175–84.
Lumeng, CN, DelProposto, JB, Westcott, DJ, et al. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes. 2008; 57: 3239–32346.
Lumeng, CN, Deyoung, SM, Saltiel, AR Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. Am J Physiol Endocrinol Metab. 2007b; 292: E166–E174.
Lundgren, M, Svensson, M, Lindmark, S, et al. Fat cell enlargement is an independent marker of insulin resistance and “hyperleptinaemia”. Diabetologia. 2007; 50: 625–33.
Mariman, ECM, Wang, P Adipocyte extracellular matrix composition, dynamics and role in obesity. Cell Mol Life Sci. 2010; 67: 1271–92.
De Matteis, R, Ricquier, D, Cinti, S TH-, NPY-, SP-, and CGRP-immunoreactive nerves in interscapular brown adipose tissue of adult rats acclimated at different temperatures: an immunohistochemical study. J Neurocytol. 1998; 27: 877–86.
Mejhert, N, Wilfling, F, Esteve, D, et al. Semaphorin 3C is a novel adipokine linked to extracellular matrix composition. Diabetologia. 2013; 56: 1792–801.
Miller, NE, Michel, CC, Nanjee, MN, et al. Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport. Am J Physiol Endocrinol Metab. 2011; 301: E659–E667.
Moreno-Aliaga, MJ, Pérez-Echarri, N, Marcos-Gómez, B, et al. Cardiotrophin-1 is a key regulator of glucose and lipid metabolism. Cell Metab. 2011; 14: 242–53.
Mori, S, Kiuchi, S, Ouchi, A, et al. Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue. Int J Biol Sci. 2014; 10: 825–33.
Murano, I, Barbatelli, G, Giordano, A, et al. Noradrenergic parenchymal nerve fiber branching after cold acclimatisation correlates with brown adipocyte density in mouse adipose organ. J Anat. 2009; 214: 171–8.
Muzik, O, Mangner, TJ, Leonard, WR, et al. 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med. 2013; 54: 523–31.
Néchad, M, Ruka, E, Thibault, J Production of nerve growth factor by brown fat in culture: relation with the in vivo developmental stage of the tissue. Comp Biochem Physiol Comp Physiol. 1994; 107: 381–8.
Nedergaard, J, Bengtsson, T, Cannon, B, et al. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007; 293: E444–E452.
Nguyen, KD, Qiu, Y, Cui, X, et al. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature. 2011; 480: 104–8.
Niijima, A Reflex effects from leptin sensors in the white adipose tissue of the epididymis to the efferent activity of the sympathetic and vagus nerve in the rat. Neurosci Lett. 1999; 262: 125–8.
Nijhuis, J, Rensen, SS, Slaats, Y, et al. Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obes (Silver Spring). 2009; 17: 2014–8.
Odegaard, JI, Ricardo-Gonzalez, RR, Goforth, MH, et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature. 2007; 447: 1116–20.
Orava, J, Nuutila, P, Lidell, ME, et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 2011; 14: 272–9.
Orava, J, Nuutila, P, Noponen, T, et al. Blunted metabolic responses to cold and insulin stimulation in brown adipose yissue of obese humans. Obesity. 2013;
Ouchi, N, Kobayashi, H, Kihara, S, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004; 279: 1304–9.
Ouellet, V, Routhier-Labadie, A, Bellemare, W, et al. Outdoor temperture, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab. 2011; 96: 192–9.
Peeraully, MR, Jenkins, JR, Trayhurn, P, et al. NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines. Am J Physiol Endocrinol Metab. 2004; 287: E331–E339.
Pellegrinelli, V, Heuvingh, J, du Roure, O, et al. Human adipocyte function is impacted by mechanical cues. J Pathol. 2014a; 233: 183–95.
Pellegrinelli, V, Rouault, C, Veyrie, N, et al. Endothelial cells from visceral adipose tissue disrupt adipocyte functions in a three-dimensional setting: partial rescue by angiopoietin-1. Diabetes. 2014b; 63: 535–49.
Permana, PA, Menge, C, Reaven, PD Macrophage-secreted factors induce adipocyte inflammation and insulin resistance. Biochem Biophys Res Commun. 2006; 341: 507–14.
Pond, CM Adipose tissue and the immune system. Prostaglandins Leukot Essent Fat Acids. 2005; 73: 17–30.
Potenza, MA, Addabbo, F, Montagnani, M Vascular actions of insulin with implications for endothelial dysfunction. Am J Physiol Endocrinol Metab. 2009; 297: E568–5677.
Puigserver, P, Wu, Z, Park, CW, et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998; 92: 829–39.
Purkayastha, S, Cai, D Neuroinflammatory basis of metabolic syndrome. Mol Metab. 2013; 2: 356–63.
Qiu, Y, Nguyen, KD, Odegaard, JI, et al. Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell. 2014; 157: 12921–308.
Rabelo, R, Reyes, C, Schifman, A, et al. Interactions among receptors, thyroid hormone response elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone. Endocrinology. 1996; 137: 3478–87.
Rao, RR, Long, JZ, White, JP, et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell. 2014; 157: 1279–91.
Rask-Madsen, C, Domínguez, H, Ihlemann, N, et al. Tumor necrosis factor-alpha inhibits insulin’s stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans. Circulation. 2003; 108: 1815–21.
Roberts, LD, Ashmore, T, Kotwica, AO, et al. Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway. Diabetes. 2014a; [Epub ahead of print].
Roberts, LD, Boström, P, O’Sullivan, JF, et al. β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab. 2014b; 19: 96–108.
Rodríguez Fernández, JL, Ben-Ze’ev, A Regulation of fibronectin, integrin and cytoskeleton expression in differentiating adipocytes: inhibition by extracellular matrix and polylysine. Differentiation. 1989; 42: 65–74.
Rosen, ED, MacDougald, OA Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 2006; 7: 885–96.
Rosen, ED, Spiegelman, BM Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol. 2000; 16: 145–71.
Rosenwald, M, Perdikari, A, Rülicke, T, et al. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol. 2013; 15: 659–67.
Rothwell, NJ, Stock, MJ Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour. Clin Sci. 1983; 64: 19–23.
Rouault, C, Pellegrinelli, V, Schilch, R, et al. Roles of chemokine ligand-2 (CXCL2) and neutrophils in influencing endothelial cell function and inflammation of human adipose tissue. Endocrinology. 2013; 154: 1069–79.
Ryu, V, Garretson, JT, Liu, Y, et al. Brown adipose tissue has sympathetic-sensory feedback circuits. J Neurosci. 2015; 35: 2181–90.
Saganami, T, Nishida, J, Ogawa, Y A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Aterioscler Thromb Vasc Biol. 2005; 25: 2062–2–68.
Sbarbati, A, Accorsi, D, Benati, D, et al. Subcutaneous adipose tissue classification. Eur J Histochem. 2010; 54: e48.
Seale, P, Bjork, B, Yang, W, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008; 454: 961–7.
Seale, P, Conroe, HM, Estall, J, et al. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest. 2011; 121: 53–6.
Serradeil-Le Gal, C, Lafontan, M, Raufaste, D, et al. Characterization of NPY receptors controlling lipolysis and leptin secretion in human adipocytes. FEBS Lett. 2000; 475: 150–6.
Shimizu, I, Aprahamian, T, Kikuchi, R, et al. Vascular rarefaction mediates whitening of brown fat in obesity. J Clin Invest. 2014; 124: 2099–112.
Skarulis, MC, Celi, FS, Mueller, E, et al. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J Clin Endocr Metab. 2010; 95: 256–62.
Skurk, T, Alberti-Huber, C, Herder, C, et al. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab. 2007; 92: 1023–33.
Søndergaard, E, Gormsen, LC, Christensen, MH, et al. Chronic adrenergic stimulation induces brown adipose tissue differentiation in visceral adipose tissue. Diabet Med. 2014; doi: 10.1111/dme.12595.
Springer, TA Adhesion receptors of the immune system. Nature. 1990; 346: 425–34.
Strissel, KJ, Stancheva, Z, Miyoshi, H, et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes. 2007; 56: 2910–8.
Sun, K, Park, J, Gupta, OT, et al. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction. Nat Commun. 2014; 5: 3485.
Sundberg, C, Kowanetz, M, Brown, LF, et al. Stable expression of angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Invest. 2002; 82: 387–401.
Tang, Q-Q, Otto, TC, Lane, MD Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. PNAS. 2004; 101: 9607–11.
Tang, W, Zeve, D, Suh, JM, et al. White fat progenitor cells reside in the adipose vasculature. Science. 2008; 322: 583–6.
Tchernof, A, Bélanger, C, Morisset, A-S, et al. Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution. Diabetes. 2006; 55: 1353–60.
Tchernof, A, Després, J-P Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013; 93: 359–404.
Tracy, TF Editorial: Acute pancreatitis and neutrophil gelatinase MMP9: don’t get me started! J Leukoc Biol. 2012; 91: 682–4.
Traktuev, DO, Merfeld-Clauss, S, Li, J, et al. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res. 2008; 102: 77–85.
Tran, K, Gealekman, O, Frontini, A, et al. The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab. 2012; 15: 222–9.
Tseng, Y-H, Kokkotou, E, Schulz, TJ, et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008; 454: 1000–4.
Tupone, D, Madden, CJ, Morrison, SF Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis. Front Neurosci. 2014; 8: 14.
Vallerand, AL, Lupien, J, Bukowiecki, LJ Cold exposure reverses the diabetogenic effects of high-fat feeding. Diabetes. 1986; 35: 329–34.
Valverde, AM Role of insulin in the biology of the fetal brown adipocyte. Av Diabetol. 2002; 18: 145–51.
Villaret, A, Galitzky, J, Decaunes, P, et al. Adipose tissue endothelial cells from obese human subjects: differences among depots in angiogenic, metabolic, and inflammatory gene expression and cellular senescence. Diabetes. 2010; 59: 2755–63.
Virtanen, KA, Lidell, ME, Orava, J, et al. Functional brown adipose tissue in healthy adults. New Eng J Med. 2009; 360: 1518–25.
Vitali, A, Murano, I, Zingaretti, MC, et al. The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res. 2012; 53: 619–29.
Wang, G-X, Zhao, X-Y, Meng, Z-X, et al. The brown fat–enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014;
Whittle, AJ, Carobbio, S, Martins, L, et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell. 2012; 149: 871–85.
Xue, Y, Petrovic, N, Cao, R, et al. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab. 2009; 9: 99–109.
Yoneshiro, T, Aita, S, Matsushita, M, et al. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest. 2013; 123: 3404–8.
Yu, Q, Stamenkovic, I Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev. 2000; 14: 163–276.
Zaragosi, L-E, Ailhaud, G, Dani, C Autocrine fibroblast growth factor 2 signaling is critical for self-renewal of human multipotent adipose-derived stem cells. Stem Cells. 2006; 24: 2412–9.
Zaragosi, L-E, Wdziekonski, B, Villageois, P, et al. Activin a plays a critical role in proliferation and differentiation of human adipose progenitors. Diabetes. 2010; 59: 2513–21.
Zeyda, M, Farmer, D, Todoric, J, et al. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond). 2007; 31: 1420–8.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this entry
Cite this entry
Peirce, V., Pellegrinelli, V., Vidal-Puig, A. (2015). Adipose Structure (White, Brown, Beige). In: Ahima, R. (eds) Metabolic Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-12125-3_23-1
Download citation
DOI: https://doi.org/10.1007/978-3-319-12125-3_23-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Online ISBN: 978-3-319-12125-3
eBook Packages: Springer Reference MedicineReference Module Medicine
Publish with us
Chapter history
-
Latest
Adipose Structure (White, Brown, Beige)- Published:
- 27 July 2023
DOI: https://doi.org/10.1007/978-3-319-12125-3_23-2
-
Original
Adipose Structure (White, Brown, Beige)- Published:
- 09 July 2015
DOI: https://doi.org/10.1007/978-3-319-12125-3_23-1