Abstract
In rats and mice the adipose organ consists of several subcutaneous and visceral depots. Some areas of these depots are brown and correspond to brown adipose tissue, while most are white and correspond to white adipose tissue. The number of brown adipocytes found in white areas varies with age, strain and environmental conditions. Brown and white adipocyte precursors are morphologically dissimilar. Together with a rich vascular supply, brown areas receive abundant noradrenergic parenchymal innervation. The gross anatomy and histology of the organ vary considerably in different physiological (cold acclimation, warm acclimation, fasting, lactation) and pathological (obesity) conditions, and many important genes, such as leptin and uncoupling protein 1, are also expressed differently in the two cell types. These basic mechanisms should be taken into account when addressing the physiopathology of obesity and its treatment.
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Wells H.G.: Adipose tissue: a neglected subject. JAMA, 114, 2177–2183, 1940.
Hsu S.M., Raine L., Fanger H.: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP procedures). J. Histochem. Cytochem., 29, 577–580, 1981.
Boss O., Samec S., Paolont-Giacobino A., Rossier C., Dulloo A., Seydoux J., Muzzin P., Giacobino J.-P.: Uncoupling protein 3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett., 408, 39–42, 1997.
Fleury C., Neverova M., Collins S., Raimbault S., Champigny O., Levi-Meyrueis C., Bouillaud F., Seldin M.F., Surwit B.S., Ricquier D., Warden C.H.: Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat. Genet., 15, 269–272, 1997.
Girardier L., Stock M.J.: Mammalian Thermogenesis. London, Chapman and Hall, 1983.
Trayhurn, P., Nicholls D.G.: Brown adipose tissue. London, Edward Arnold, 1986.
Cinti S.: Morphological and functional aspects of brown adipose tissue. In: Giorgi P.L., Suskind B.M., Catassi C. (Eds.), The obese child. vol 2. Basel, Karger, 1992, pp. 115–124.
Cinti S.: The Adipose Organ. Milano, Editrice Kurtis, 1999.
Cannon B., Hedin A., Nedergaard J.: Exclusive occurrence of thermogenin antigen in brown adipose tissue. FEBS Lett., 150, 129–132, 1982.
Cinti S., Zancanaro C., Sbarbati A., Cigolini M., Vogel P., Ricquier D., Fakan S.: Immunoelectron microscopical identification of the uncoupling protein in brown adipose tissue mitochondria. Biol. Cell, 67, 359–362, 1989.
Klaus S., Casteilla L., Bouillaud F., Ricquier D.: The uncoupling protein UCP: a membraneous mitochondrial ion carrier exclusively expressed in brown adipose tissue. Int. J. Biochem., 23, 791–801, 1991.
Nnodim J.O., Lever J.D.: Neural and vascular provisions of rat interscapular brown adipose tissue. Am. J. Anat., 182, 283–293, 1988.
Foster D.O., Depocas F., Zaror-Beherens G.: Unilaterality of the sympathetic innervation of each pad of rat interscapular brown adipose tissue. Can. J. Physiol. Pharmacol., 60, 107–113, 1982.
Norman D., Mukherjee S., Symons D., Jung R.T., Lever J.D.: Neuropeptides in interscapular and perirenal brown adipose tissue in the rat: a plurality of innervation. J. Neurocytol., 17, 305–311, 1988.
Gibson S.J., Polak J.M., Bloom S.R., Sabate I.M., Mulderry P.M., Ghatei M.A., McGregor G.P., Morrison J.E.B., Kelly J.S., Evans R.M., Rosenfeld M.G.: Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and eight other species. J. Neurosci., 4, 3101–3111, 1984.
Skofitsch F., Jacobowitz D.M.: Calcitonin gene-related peptide coexists with substance P in capsaicin sensitive neurons and sensory ganglia of the rat. Peptides, 6, 747–754, 1985.
Terenghi G., Polak J.M., Ghatei M.A., Mulderry P.K., Butler J.M., Unger W.G., Bloom S.R.: Distribution and origin of CGRP-immunoreactivity in the sensory innervation of the mammalian eye. J. Comp. Neurol., 233, 505–516, 1985.
Lee Y., Kaway Y., Shiosaka S., Takami K., Kiyama H., Hylliard C., McIntyre L, Emson P.C., Tohyama M.: Coexistence of calcitonin gene-related peptide and substance P-like peptide in single cells of the trigeminal ganglion of the rat: Immunohistochemical analysis. Brain Res., 330, 194–196, 1986.
Cannon B., Nedergaard J., Lundberg J.M., Hokfelt T., Terenius L., Goldstein M.: “Neuropeptide tyrosine” (NPY) is co-stored with noradrenaline in vascular but not in parenchymal sympathetic nerves of brown adipose tissue. Exp. Cell Res., 164, 546–550, 1986.
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., 27, 877–886, 1998.
Schneider-Picard G., Carpentier J.L., Orci L.: Quantitative evaluation of gap junctions during development of the brown adipose tissue. J. Lipid Res., 21, 600–607, 1980.
Moncada S., Higgs A.: The L-arginine-nitric oxide pathway. N. Engl. J. Med., 329, 2002–2012, 1993.
Nisoli E., Tonello C., Briscini L., Carruba M.: Inducible nitric oxide synthase in rat brown adipocytes: implications for blood flow to brown adipose tissue. Endocrinology, 1387, 676–682, 1997.
Cinti S., Cigolini M., Bosello O., Björntorp P.: A morphological study of the adipocyte precursor. J. Submicr. Cytol., 16, 243–251, 1984.
Cinti S., Cigolini M., Sbarbati A., Zancanaro C.: Ultrastructure of brown adipocytes mitochondria in cell culture from explants. J. Submicr. Cytol., 18, 625–627, 1986.
Cinti S., Cigolini M., Sbarbati A., Zancanaro C., Björntorp P.: Effects of noradrenaline exposure on rat brown adipocytes in cultures. An ultrastructural study. Tissue Cell, 19, 809–816, 1987.
Sbarbati A., Zancanaro C., Cigolini M., Cinti S.: Brown adipose tissue: a scanning electron microscopy study of tissue and cultured adipocytes. Acta Anat., 128, 84–88, 1987.
Néchad M.: Development of brown fat cells in monolayer culture. II. Ultrastructural characterization of precursors, differentiating adipocytes and their mitochondria. Exp. Cell Res., 149, 119–127, 1983.
Cigolini M., Cinti S., Brunetti L., Bosello O., Osculati F., Björntorp P.: Human brown adipose cells in culture. Exp. Cell Res., 159, 261–266, 1985.
Cigolini M., Cinti S., Bosello O., Brunetti L., Björntorp P.: Isolation and ultrastructural features of brown adipocytes in culture. J. Anat., 145, 207–216, 1986.
Rehnmark S., Kopecky J., Jacobsson A., Néchad M., Herron D., Nelson B.D., Obregon MJ., Nedergaard J., Cannon B.: Brown adipocytes differentiated in vitro can express the gene for the uncoupling protein themogenin: effects of hypothyroidism and norepinephrine. Exp. Cell Res., 182, 75–83, 1989.
Klaus S., Cassard-Doulcier A.M., Ricquier D.: Development of Phodopus sungorus brown preadipocytes in primary cell cultures: effect of an atypical beta-adrenergic agonist insulin, and tiiiodothyronine on differentiation, mitochondrial development, and expression of the uncoupling protein UCP. J. Cell Biol., 115, 1783–1790, 1991.
Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J.M.: Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425–432, 1994.
Frederich R.C., Lollmann B., Hamann A., Napolitano-Rosen A., Kahan B.B., Lowell B.B., Flier J.S.: Expression of the ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. J. Clin. Invest., 96, 1658–1663, 1995.
Blum W.F., Mess W., Rascher W.: Leptin: The Voice of Adipose Tissue. Heidelberg, JAB Verlag, 1997.
Cinti S., De Matteis R., Zingaretti M.C., Himms-Hagen J.: Immunohistochemical localization of leptin in adipose tissues. In: Blum W.F., Kiess W., Rascher W., Barth J.A. (Eds.), Leptin - The voice of adipose tissue. Heidelberg, Verlag Edition J. & J, 1997, pp. 78–82.
De Matteis R., Dashtipour K., Ognibene A., Cinti S.: Localization of leptin receptor splice variants in mouse peripheral tissues by immunohistochemistry. Proceedings of the Nutrition Society, 57, 441–448, 1989.
De Matteis R., Cinti S.: Ultrastructural immunolocalisation of leptin receptor in mouse brain. Neuroendocrinology, 68, 412–419, 1998.
Spiegelman B.M., Flier J.S.: Adipogenesis and obesity: rounding out the big picture. Cell, 87, 377–389, 1996.
Flier J.S.: The adipocyte: storage depot or node on the energy information superhighway. Cell, 80, 15–18, 1995.
Casanueva F.F., Dieguez C.: Neuroendocrine regulation and actions of leptin. Front. Neuroendocrinol., 20, 317–363, 1999.
Crandall D.L., Hausman G.J., Kral J.G.: A review of the microcirculation of adipose tissue: anatomic, metabolic and angiogenic perspectives. Microcirculation, 4, 211–232, 1997.
Cinti S., Ebeerbach S., Castellucci M., Accili D.: Lack of insulin receptors affects the formation of white adipose tissue in mice. A morphometric and ultrastructural analysis. Diabetologia, 41, 171–177, 1998.
Pierleoni C., Verdenelli F., Castellucci M., Cinti S.: Fibronectins and basal lamina molecules expression in human subcutaneous white adipose tissue. Eur. J. Histochem., 42, 183–188, 1998.
Fawcett D.W.: A comparison of the histological organization and histochemical reactions of brown fat and ordinary fat. J. Morphol., 90, 363–372, 1952.
Giordano A., Morroni M., Santone G., Marchesi G.F., Cinti S.: 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., 25, 125–136, 1996.
Cinti S., Cigolini M., Morroni M., Zingaretti M.C.: S-100 protein in white preadipocytes: an immunoelectronmicroscopic study. Anal. Rec., 224, 466–472, 1989.
Barbatelli G., Morroni M., Vinesi P., Cinti S., Michetti F.: S-100 protein in rat brown adipose tissue under different functional conditions: A morphological, immunocytochemical, and immunochemical study. Exp. Cell Res., 208, 226–231, 1993.
Ailhaud G., Dani C., Gaillard D., Grimaldi P., Negrel R.: Critical steps and hormonal control of adipose cell differentiation. In: Giorgi P.L., Suskind R.M., Catassi C. (Eds.), The obese child. vol 2. Basel, Karger, 1992, pp. 115–124.
Cinti S., Cigolini M., Gazzanelli G., Bosello O.: An ultrastructural study of adipocyte precursors from epididymal fat pads of adult rats in culture. J. Submicr. Cytol., 17, 631–636, 1985.
Maffei M., Fei H., Lee G.H., Dani C., Leroy P., Zhang Y., Proenca R., Negrel R., Ailhaud G., Friedman J.M.: Increased expression in adipocytes of ob mRNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc. Natl. Acad. Sci. USA, 929, 6957–6960, 1995.
Young P., Arch J.R.S., Ashwell M.: Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Lett., 167, 10–14, 1984.
Loncar D.: Convertible adipose tissue in mice. Cell Tissue Res., 266, 149–161, 1991.
Cousin B., Cinti S., Morroni M., Raimbault S., Ricquier D., Penicaud L., Casteilla L.: Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J. Cell Sci., 103, 931–942, 1992.
Himms-Hagen J., Ricquier D.: Brown adipose tissue. In: Bray G.A., Bouchard C., James W.P.T. (Eds.), Handbook of Obesity. New York, Marcel Dekker, 1998, pp. 415–441.
Mory G., Bouillaud F., Combes-George M., Ricquier D.: Noradrenaline controls the concentration of the uncoupling protein in brown adipose tissue. FEBS Lett., 166, 39–396, 1984.
Tsuhazaki K., Nikami H., Shimizu Y., Kawada T., Yoshida T., Saito M.: Chronic administration of beta-adrenergic agonists can mimic the stimulative effect of cold exposure on protein synthesis in rat brown adipose tissue. J. Biochem., 117, 96–100, 1995.
Geloen A, Collet A.J., Bukowiecki L.J.: Role of sympathetic innervation in brown adipocyte proliferation. Am. J. Physiol., 263, R1176–R1181, 1992.
Lafontan M., Berlan M.: Fat cells adrenergic receptors and the control of white and brown fat cells functions. J. Lipid Res., 34, 1057–1091, 1993.
Arch J.R.S., Kaumann A.J.: Beta3 and atypical beta-adrenoceptors. Med. Res. Rev., 13, 663–729, 1993.
Giacobino J.-P.: Beta3 adrenoceptor: an update. Eur. J. Endocrinol., 132, 377–385, 1995.
Sbarbati A., Morroni M., Zancanaro C., Cinti S.: Rat interscapular brown adipose tissue at different ages: a morphometric study. Int. J. Obesity, 15, 581–588, 1991.
Morroni M., Barbatelli G., Zingaretti M.C., Cinti S.: Immunohistochemical, ultrastrucrural and morphometric evidence for brown adipose tissue recruitment due to cold acclimation in old rats. Int. J. Obesity, 19, 126–131, 1995.
Barbatelli G., Heinzelmann M., Ferrara P., Morroni M., Cinti S.: Quantitative evaluations of gap junctions in old rat brown adipose tissue after cold acclimation: a freeze-fracture and ultrastructural study. Tissue Cell, 26, 667–676, 1994.
Cousin B., Casteilla L., Darn C., Muzzin P., Revelli J-P., Penicaud L.: Adipose tissue from various anatomical size are characterized by different patterns of gene expression and regulation. Biochem. J., 292, 873–876, 1993.
Holzer P.: Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin generelated peptide and other neuropeptides. Neuroscience, 24, 739–768, 1988.
Caterina M.J., Schumaker M.A., Tominaga M., Rosen T.A., Levine J.D., Julius D.: The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 389, 816–824, 1997.
Giordano A., Morroni M., Carle F., Gesuita R., Marchesi G.F., Cinti S.: Sensory nerves affect the recruitment and differentiation of rat periovarian brown adipocytes during cold acclimation. J. Cell Sci., 111, 2587–2594, 1998.
Himms-Hagen J., Melnyk A., Zingaretti M.C., Ceresi E., Barbatelli G., Cinti S.: Multilocular adipocytes in white adipose tissue of CL316,243-treated rats derive directly from white adipocytes. Am. J. Physiol., 279, C670–C681, 2000.
Cinti S., De Matteis R., Zingareth M.C., Cancello R., Himms-Hagen J., Ricquier D.: Harlequin’s secret: UCP-immunostained brown adipose tissue. Int. J. Obesity, 21 (Suppl. 2), S47, 1997.
Cancello R., Zingareth M.C., Sarzani R., Ricquier D., Cinti S.: Leptin and UCP1 genes are reciprocally regulated in brown adipose tissue. Endocrinology, 139, 4747–4750, 1998.
Himms-Hagen J.: Obesity may be due to malfunctioning of brown fat. Can. Med. Assoc. J. 121, 1361–1364, 1979.
Rothwell N.J., Stock M.J.: A role for brown adipose tissue in diet-induced thermogenesis. Nature, 281, 31–35, 1979.
Lowell B.B., Susulic V.S., Hamann A., Lawitts J.A., Himms-Hagen J., Boyer B.B., Kozak L., Flier J.S.: Development of morbid obesity in transgenic mice following the genetic ablation of brown adipose tissue. Nature, 366, 740–742, 1993.
Cinti S., Frederich R.C., Zingaretti M.C., De Matteis R., Flier J.S., Lowell B.B.: Immunohistochemical localization of leptin and uncoupling protein in white and brown adipose tissue. Endocrinology, 138, 797–804, 1997.
Blanchette-Mackie E.J., Scow R.O.: Lipolysis and lamellar structures in white adipose tissue of young rats: lipid movement in membranes. J. Ultrastruct Res., 77, 295–318, 1981.
Blanchette-Mackie E.J., Scow R.O.: Movement of lipolytic products to mitochondria in brown adipose tissue of young rats: an electron microscope study. J. Lipid Res., 24, 229–244, 1983.
Chan E., Swaminathan R.: Role of prolactin in lactation-induced changes in brown adipose tissue. Am. J. Physiol., 258, R51–R56, 1990.
Dalquest W.W., Werner H.J.: The interscapular gland of a tropical fruit bat. Anat. Rec., 111, 345–353, 1951.
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Cinti, S. Anatomy of the adipose organ. Eat Weight Disord 5, 132–142 (2000). https://doi.org/10.1007/BF03354443
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DOI: https://doi.org/10.1007/BF03354443