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Angiogenesis in Adipose Tissue pp 103–129Cite as

Lymphatic System in Adipose Tissues

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Abstract

The lymphatic system is uniquely aligned to integrate with many organ systems. Originally discovered as a vessel network separate from the circulatory system, it took centuries before the lymphatic system was given the attention it truly deserves. Within the last 2 decades, a resurgence of literature has revealed the lymphatic system to be intimately linked to tissue fluid homeostasis, immune cell trafficking, and nutrient absorption. Particularly, the lymphatic system within the digestive system is specially devoted to transport absorbed lipids, making it an important organ system in adipose tissue biology. This chapter will review the origins and structural organization of the lymphatic system, followed by the key events taking place in the development of new lymphatic vessels, or lymphangiogenesis. The biological links between the lymphatic system and the adipose tissue will be further highlighted, with emphasis on its functional relevance. Finally, the implications of dysfunctions of the lymphatic system will be considered in relation to adipose tissue disorders.

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References

  • Alexander JS, Ganta VC, Jordan PA, Witte MH. Gastrointestinal lymphatics in health and disease. Pathophysiology. 2010;17(4):315–35.

    PubMed  CAS  Google Scholar 

  • Aschen S, Zampell JC, Elhadad S, Weitman E, De Brot M, Mehrara BJ. Regulation of adipogenesis by lymphatic fluid stasis: part II. Expression of adipose differentiation genes. Plast Reconstr Surg. 2012;129(4):838–47.

    PubMed  CAS  Google Scholar 

  • Aghamohammadzadeh R, Withers S, Lynch F, Greenstein A, Malik R, Heagerty A. Perivascular adipose tissue from human systemic and coronary vessels: the emergence of a new pharmacotherapeutic target. Br J Pharmacol. 2012;165(3):670–82.

    PubMed  CAS  Google Scholar 

  • Arngrim N, Simonsen L, Holst JJ, Bulow J. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: a possible link between obesity and local tissue inflammation? Int J Obes (Lond). 2013;37(5):748–50.

    CAS  Google Scholar 

  • Abtahian F, Guerriero A, Sebzda E, Lu MM, Zhou R, Mocsai A, et al. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science. 2003;299(5604):247–51.

    PubMed  CAS  Google Scholar 

  • Acedo SC, Gotardo EM, Lacerda JM, de Oliveira CC, de Oliveira CP, Gambero A. Perinodal adipose tissue and mesenteric lymph node activation during reactivated TNBS-colitis in rats. Dig Dis Sci. 2011;56(9):2545–52.

    PubMed  CAS  Google Scholar 

  • Albrecht I, Christofori G. Molecular mechanisms of lymphangiogenesis in development and cancer. Int J Dev Biol. 2011;55(4–5):483–94.

    PubMed  CAS  Google Scholar 

  • Arkill KP, Moger J, Winlove CP. The structure and mechanical properties of collecting lymphatic vessels: an investigation using multimodal nonlinear microscopy. J Anat. 2010;216(5):547–55.

    PubMed  Google Scholar 

  • Bierman HR, Byron Jr RL, Kelly KH, Gilfillan RS, White LP, Freeman NE, et al. The characteristics of thoracic duct lymph in man. J Clin Invest. 1953;32(7):637–49.

    PubMed  CAS  Google Scholar 

  • Baluk P, Fuxe J, Hashizume H, Romano T, Lashnits E, Butz S, et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med. 2007;204(10):2349–62.

    PubMed  CAS  Google Scholar 

  • Bazigou E, Xie S, Chen C, Weston A, Miura N, Sorokin L, et al. Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev Cell. 2009;17(2):175–86.

    PubMed  CAS  Google Scholar 

  • Brorson H. From lymph to fat: complete reduction of lymphoedema. Phlebology. 2010;25 Suppl 1:52–63.

    PubMed  Google Scholar 

  • Bjorndahl M, Cao R, Nissen LJ, Clasper S, Johnson LA, Xue Y, et al. Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo. Proc Natl Acad Sci U S A. 2005;102(43):15593–8.

    PubMed  Google Scholar 

  • Bock F, Onderka J, Dietrich T, Bachmann B, Pytowski B, Cursiefen C. Blockade of VEGFR3-signalling specifically inhibits lymphangiogenesis in inflammatory corneal neovascularisation. Graefes Arch Clin Exp Ophthalmol. 2008;246(1):115–9.

    PubMed  CAS  Google Scholar 

  • Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, et al. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest. 2005;115(2):247–57.

    PubMed  CAS  Google Scholar 

  • Barbier M, Vidal H, Desreumaux P, Dubuquoy L, Bourreille A, Colombel JF, et al. Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases. Gastroenterol Clin Biol. 2003;27(11):987–91.

    PubMed  CAS  Google Scholar 

  • Burton JB, Priceman SJ, Sung JL, Brakenhielm E, An DS, Pytowski B, et al. Suppression of prostate cancer nodal and systemic metastasis by blockade of the lymphangiogenic axis. Cancer Res. 2008;68(19):7828–37.

    PubMed  CAS  Google Scholar 

  • Bruemmer D. Targeting angiogenesis as treatment for obesity. Arterioscler Thromb Vasc Biol. 2012;32(2):161–2.

    PubMed  CAS  Google Scholar 

  • Cruikshank W. The anatomy of the absorbing vessels of the human body. London; 1786.

    Google Scholar 

  • Costa M, Funess JB. Observations on the anatomy and amine histochemistry of the nerves and ganglia which supply the pelvic viscera and on the associated chromaffin tissue in the guinea-pig. Z Anat Entwicklungsgesch. 1973;140(1):85–108.

    PubMed  CAS  Google Scholar 

  • Clark ER, Clark EL. Microscopic studies of new formation of fat in living adult rabbits. Am J Anat. 1940;67:255–81.

    Google Scholar 

  • Chikly B. Who discovered the lymphatic system. Lymphology. 1997;30(4):186–93.

    PubMed  CAS  Google Scholar 

  • Cho CH, Koh YJ, Han J, Sung HK, Jong Lee H, Morisada T, et al. Angiogenic role of LYVE-1-positive macrophages in adipose tissue. Circ Res. 2007;100(4):e47–57.

    PubMed  CAS  Google Scholar 

  • Chen Y, Yu G, Ding H. Lymphangiogenic and angiogentic microvessel density in gallbladder carcinoma. Hepatogastroenterology. 2011;58(105):20–5.

    PubMed  Google Scholar 

  • Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011;12(11):722–34.

    PubMed  CAS  Google Scholar 

  • Cox R, Garcia-Palmieri MR. Chapter 31: cholesterol, triglycerides, and associated lipoproteins. In: Walker H, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations. 3rd ed. Boston: Butterworths; 1990.

    Google Scholar 

  • Davis MJ, Davis AM, Lane MM, Ku CW, Gashev AA. Rate-sensitive contractile responses of lymphatic vessels to circumferential stretch. J Physiol. 2009;587(Pt 1):165–82.

    PubMed  CAS  Google Scholar 

  • Drayson MT, Ford WL. Afferent lymph and lymph borne cells: their influence on lymph node function. Immunobiology. 1984;168(3–5):362–79.

    PubMed  CAS  Google Scholar 

  • Da MX, Wu XT, Wang J, Guo TK, Zhao ZG, Luo T, et al. Expression of cyclooxygenase-2 and vascular endothelial growth factor-C correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer. Arch Med Res. 2008;39(1):92–9.

    PubMed  CAS  Google Scholar 

  • Deng J, Liang H, Sun D, Pan Y, Wang B, Guo Y. Vascular endothelial growth factor-D is correlated with hepatic metastasis from gastric cancer after radical gastrectomy. Surgery. 2009;146(5):896–905.

    PubMed  Google Scholar 

  • Drevon CA. Fatty acids and expression of adipokines. Biochim Biophys Acta. 2005;1740(2):287–92.

    PubMed  CAS  Google Scholar 

  • Drabkin HA, Gemmill RM. Obesity, cholesterol, and clear-cell renal cell carcinoma (RCC). Adv Cancer Res. 2010;107:39–56.

    PubMed  CAS  Google Scholar 

  • Elias RM, Johnston MG. Modulation of fluid pumping in isolated bovine mesenteric lymphatics by a thromboxane/endoperoxide analogue. Prostaglandins. 1988;36(1):97–106.

    PubMed  CAS  Google Scholar 

  • Enholm B, Karpanen T, Jeltsch M, Kubo H, Stenback F, Prevo R, et al. Adenoviral expression of vascular endothelial growth factor-C induces lymphangiogenesis in the skin. Circ Res. 2001;88(6):623–9.

    PubMed  CAS  Google Scholar 

  • Ferguson MK, DeFilippi VJ, Reeder LB. Characterization of contractile properties of porcine mesenteric and tracheobronchial lymphatic smooth muscle. Lymphology. 1994;27(2):71–81.

    PubMed  CAS  Google Scholar 

  • Fang J, Dagenais SL, Erickson RP, Arlt MF, Glynn MW, Gorski JL, et al. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet. 2000;67(6):1382–8.

    PubMed  CAS  Google Scholar 

  • Gashev AA, Davis MJ, Zawieja DC. Inhibition of the active lymph pump by flow in rat mesenteric lymphatics and thoracic duct. J Physiol. 2002;540(Pt 3):1023–37.

    PubMed  CAS  Google Scholar 

  • Gasheva OY, Zawieja DC, Gashev AA. Contraction-initiated NO-dependent lymphatic relaxation: a self-regulatory mechanism in rat thoracic duct. J Physiol. 2006;575(Pt 3):821–32.

    PubMed  CAS  Google Scholar 

  • Gao Y, Zhong WX, Mu DB, Yuan YP, Zhang YH, Yu JM, et al. Distributions of angiogenesis and lymphangiogenesis in gastrointestinal intramucosal tumors. Ann Surg Oncol. 2008;15(4):1117–23.

    PubMed  Google Scholar 

  • Guo X, Chen Y, Xu Z, Qian Y, Yu X. Prognostic significance of VEGF-C expression in correlation with COX-2, lymphatic microvessel density, and clinicopathologic characteristics in human non-small cell lung cancer. Acta Biochim Biophys Sin (Shanghai). 2009;41(3):217–22.

    CAS  Google Scholar 

  • Grigorova IL, Panteleev M, Cyster JG. Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure. Proc Natl Acad Sci U S A. 2010;107(47):20447–52.

    PubMed  CAS  Google Scholar 

  • Geleff S, Schoppmann SF, Oberhuber G. Increase in podoplanin-expressing intestinal lymphatic vessels in inflammatory bowel disease. Virchows Arch. 2003;442(3):231–7.

    PubMed  Google Scholar 

  • Guerre-Millo M. Adipose tissue and adipokines: for better or worse. Diabetes Metab. 2004;30(1):13–9.

    PubMed  CAS  Google Scholar 

  • Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.

    PubMed  CAS  Google Scholar 

  • Huxley VH, Scallan J. Lymphatic fluid: exchange mechanisms and regulation. J Physiol. 2011;589(Pt 12):2935–43.

    PubMed  CAS  Google Scholar 

  • Hargens AR, Zweifach BW. Contractile stimuli in collecting lymph vessels. Am J Physiol. 1977;233(1):H57–65.

    PubMed  CAS  Google Scholar 

  • Hukkanen M, Konttinen YT, Terenghi G, Polak JM. Peptide-containing innervation of rat femoral lymphatic vessels. Microvasc Res. 1992;43(1):7–19.

    PubMed  CAS  Google Scholar 

  • Hodis J, Vaclavikova R, Farghali H. Beta-3 agonist-induced lipolysis and nitric oxide production: relationship to PPARgamma agonist/antagonist and AMP kinase modulation. Gen Physiol Biophys. 2011;30(1):90–9.

    PubMed  CAS  Google Scholar 

  • Harford KA, Reynolds CM, McGillicuddy FC, Roche HM. Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc. 2011;70(4):408–17.

    PubMed  CAS  Google Scholar 

  • Harvey NL, Srinivasan RS, Dillard ME, Johnson NC, Witte MH, Boyd K, et al. Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat Genet. 2005;37(10):1072–81.

    PubMed  CAS  Google Scholar 

  • Hwang JH, Kim IG, Lee JY, Piao S, Lee DS, Lee TS, et al. Therapeutic lymphangiogenesis using stem cell and VEGF-C hydrogel. Biomaterials. 2011;32(19):4415–23.

    PubMed  CAS  Google Scholar 

  • Halin C, Fahrngruber H, Meingassner JG, Bold G, Littlewood-Evans A, Stuetz A, et al. Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. Am J Pathol. 2008;173(1):265–77.

    PubMed  CAS  Google Scholar 

  • Hopfl G, Ogunshola O, Gassmann M. HIFs and tumors–causes and consequences. Am J Physiol Regul Integr Comp Physiol. 2004;286(4):R608–23.

    PubMed  Google Scholar 

  • Johnston MG, Gordon JL. Regulation of lymphatic contractility by arachidonate metabolites. Nature. 1981;293(5830):294–7.

    PubMed  CAS  Google Scholar 

  • Johnston MG, Feuer C. Suppression of lymphatic vessel contractility with inhibitors of arachidonic acid metabolism. J Pharmacol Exp Ther. 1983;226(2):603–7.

    PubMed  CAS  Google Scholar 

  • Johnston MG, Kanalec A, Gordon JL. Effects of arachidonic acid and its cyclo-oxygenase and lipoxygenase products on lymphatic vessel contractility in vitro. Prostaglandins. 1983;25(1):85–98.

    PubMed  CAS  Google Scholar 

  • Jackson DG. Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis. APMIS. 2004;112(7–8):526–38.

    PubMed  CAS  Google Scholar 

  • Jain RK. Molecular regulation of vessel maturation. Nat Med. 2003;9(6):685–93.

    PubMed  CAS  Google Scholar 

  • Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58–62.

    PubMed  CAS  Google Scholar 

  • Junghans BM, Collin HB. Limbal lymphangiogenesis after corneal injury: an autoradiographic study. Curr Eye Res. 1989;8(1):91–100.

    PubMed  CAS  Google Scholar 

  • Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276(5317):1423–5.

    PubMed  CAS  Google Scholar 

  • Karkkainen MJ, Saaristo A, Jussila L, Karila KA, Lawrence EC, Pajusola K, et al. A model for gene therapy of human hereditary lymphedema. Proc Natl Acad Sci U S A. 2001;98(22):12677–82.

    PubMed  CAS  Google Scholar 

  • Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 2004;5(1):74–80.

    PubMed  CAS  Google Scholar 

  • Kaiserling E, Krober S, Geleff S. Lymphatic vessels in the colonic mucosa in ulcerative colitis. Lymphology. 2003;36(2):52–61.

    PubMed  CAS  Google Scholar 

  • Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S, Jaattela M, et al. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res. 2001;61(5):1786–90.

    PubMed  CAS  Google Scholar 

  • Kojima T, Azar DT, Chang JH. Neostatin-7 regulates bFGF-induced corneal lymphangiogenesis. FEBS Lett. 2008;582(17):2515–20.

    PubMed  CAS  Google Scholar 

  • Kindel T, Lee DM, Tso P. The mechanism of the formation and secretion of chylomicrons. Atheroscler Suppl. 2010;11(1):11–6.

    PubMed  CAS  Google Scholar 

  • Kohan AB, Yoder SM, Tso P. Using the lymphatics to study nutrient absorption and the secretion of gastrointestinal hormones. Physiol Behav. 2011;105(1):82–8.

    PubMed  CAS  Google Scholar 

  • Karpanen T, Alitalo K. Molecular biology and pathology of lymphangiogenesis. Annu Rev Pathol. 2008;3:367–97.

    PubMed  CAS  Google Scholar 

  • Lord RS. The white veins: conceptual difficulties in the history of the lymphatics. Med Hist. 1968;12(2):174–84.

    PubMed  CAS  Google Scholar 

  • Leak LV. The structure of lymphatic capillaries in lymph formation. Fed Proc. 1976;35(8):1863–71.

    PubMed  CAS  Google Scholar 

  • Leak LV, Burke JF. Ultrastructural studies on the lymphatic anchoring filaments. J Cell Biol. 1968;36(1):129–49.

    Google Scholar 

  • Lim HY, Rutkowski JM, Helft J, Reddy ST, Swartz MA, Randolph GJ, et al. Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. Am J Pathol. 2009;175(3):1328–37.

    PubMed  CAS  Google Scholar 

  • Lumeng CN, Deyoung SM, Bodzin JL, Saltiel AR. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes. 2007;56(1):16–23.

    PubMed  CAS  Google Scholar 

  • Lin J, Lalani AS, Harding TC, Gonzalez M, Wu WW, Luan B, et al. Inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble VEGFR-3 decoy receptor. Cancer Res. 2005;65(15):6901–9.

    PubMed  CAS  Google Scholar 

  • Mayerson HS. On lymph and lymphatics. Circulation. 1963;28:839–42.

    PubMed  CAS  Google Scholar 

  • Maruyama K, Asai J, Ii M, Thorne T, Losordo DW, D’Amore PA. Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. Am J Pathol. 2007;170(4):1178–91.

    PubMed  Google Scholar 

  • Mendoza E, Schmid-Schonbein GW. A model for mechanics of primary lymphatic valves. J Biomech Eng. 2003;125(3):407–14.

    PubMed  Google Scholar 

  • Mislin H. Active contractility of the lymphangion and coordination of lymphangion chains. Experientia. 1976;32(7):820–2.

    PubMed  CAS  Google Scholar 

  • Mislin H. Experimental detection of autochthonous automatism of lymph vessels. Experientia. 1961;17:29–30.

    PubMed  CAS  Google Scholar 

  • Muthuchamy M, Gashev A, Boswell N, Dawson N, Zawieja D. Molecular and functional analyses of the contractile apparatus in lymphatic muscle. FASEB J. 2003;17(8):920–2.

    PubMed  CAS  Google Scholar 

  • Mizuno R, Koller A, Kaley G. Regulation of the vasomotor activity of lymph microvessels by nitric oxide and prostaglandins. Am J Physiol. 1998;274(3 Pt 2):R790–6.

    PubMed  CAS  Google Scholar 

  • Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H, Tomita M, et al. Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest. 2005;115(9):2363–72.

    PubMed  CAS  Google Scholar 

  • Mattacks CA, Pond CM. Interactions of noradrenalin and tumour necrosis factor alpha, interleukin 4 and interleukin 6 in the control of lipolysis from adipocytes around lymph nodes. Cytokine. 1999;11(5):334–46.

    PubMed  CAS  Google Scholar 

  • Makinen T, Adams RH, Bailey J, Lu Q, Ziemiecki A, Alitalo K, et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev. 2005;19(3):397–410.

    PubMed  Google Scholar 

  • Michailidou Z, Turban S, Miller E, Zou X, Schrader J, Ratcliffe PJ, et al. Increased angiogenesis protects against adipose hypoxia and fibrosis in metabolic disease-resistant 11beta-hydroxysteroid dehydrogenase type 1 (HSD1)-deficient mice. J Biol Chem. 2012;287(6):4188–97.

    PubMed  CAS  Google Scholar 

  • Miller NE, Michel CC, Nanjee MN, Olszewski WL, Miller IP, Hazell M, et al. Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport. Am J Physiol Endocrinol Metab. 2011;301(4):E659–67.

    PubMed  CAS  Google Scholar 

  • Morisada T, Oike Y, Yamada Y, Urano T, Akao M, Kubota Y, et al. Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation. Blood. 2005;105(12):4649–56.

    PubMed  CAS  Google Scholar 

  • Nagahashi M, Ramachandran S, Rashid OM, Takabe K. Lymphangiogenesis: a new player in cancer progression. World J Gastroenterol. 2010;16(32):4003–12.

    PubMed  CAS  Google Scholar 

  • Nanjee MN, Cooke CJ, Wong JS, Hamilton RL, Olszewski WL, Miller NE. Composition and ultrastructure of size subclasses of normal human peripheral lymph lipoproteins: quantification of cholesterol uptake by HDL in tissue fluids. J Lipid Res. 2001;42(4):639–48.

    PubMed  CAS  Google Scholar 

  • Nakamura K, Hongo A, Kodama J, Hiramatsu Y. Fat accumulation in adipose tissues as a risk factor for the development of endometrial cancer. Oncol Rep. 2011;26(1):65–71.

    PubMed  Google Scholar 

  • Niederleithner H, Heinz M, Tauber S, Bilban M, Pehamberger H, Sonderegger S, et al. Wnt1 is anti-lymphangiogenic in a melanoma mouse model. J Invest Dermatol. 2012;132(9):2235–44.

    PubMed  CAS  Google Scholar 

  • Norrmen C, Ivanov KI, Cheng J, Zangger N, Delorenzi M, Jaquet M, et al. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. J Cell Biol. 2009;185(3):439–57.

    PubMed  CAS  Google Scholar 

  • Nougues J, Reyne Y, Dulor JP. Differentiation of rabbit adipocyte precursors in primary culture. Int J Obes. 1988;12(4):321–33.

    PubMed  CAS  Google Scholar 

  • Okada K, Osaki M, Araki K, Ishiguro K, Ito H, Ohgi S. Expression of hypoxia-inducible factor (HIF-1alpha), VEGF-C and VEGF-D in non-invasive and invasive breast ductal carcinomas. Anticancer Res. 2005;25(4):3003–9.

    PubMed  CAS  Google Scholar 

  • Oliver G. Lymphatic vasculature development. Nat Rev Immunol. 2004;4(1):35–45.

    PubMed  CAS  Google Scholar 

  • Oka M, Iwata C, Suzuki HI, Kiyono K, Morishita Y, Watabe T, et al. Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis. Blood. 2008;111(9):4571–9.

    PubMed  CAS  Google Scholar 

  • Orlov RS, Borisova RP, Mandryko ES. [The contractile and electrical activity of the smooth muscles of the major lymph vessels]. Fiziol Zh SSSR Im I M Sechenova. 1975;61(7):1045–53.

    PubMed  CAS  Google Scholar 

  • Ohhashi T, Kobayashi S, Tsukahara S, Azuma T. Innervation of bovine mesenteric lymphatics: from the histochemical point of view. Microvasc Res. 1982;24(3):377–85.

    PubMed  CAS  Google Scholar 

  • Ohtani O, Ohtani Y. Structure and function of rat lymph nodes. Arch Histol Cytol. 2008;71(2):69–76.

    PubMed  Google Scholar 

  • Plaku KJ, von der Weid PY. Mast cell degranulation alters lymphatic contractile activity through action of histamine. Microcirculation. 2006;13(3):219–27.

    PubMed  CAS  Google Scholar 

  • Pond CM. Adipose tissue: quartermaster to the lymph node garrisons. Biologist (London). 2000;47(3):147–50.

    CAS  Google Scholar 

  • Poznanski WJ, Waheed I, Van R. Human fat cell precursors. Morphologic and metabolic differentiation in culture. Lab Invest. 1973;29(5):570–6.

    PubMed  CAS  Google Scholar 

  • Piller NB. Lymphoedema, macrophages and benzopyrones. Lymphology. 1980;13(3):109–19.

    PubMed  CAS  Google Scholar 

  • Piller NB. Macrophage and tissue changes in the developmental phases of secondary lymphoedema and during conservative therapy with benzopyrone. Arch Histol Cytol. 1990;53(Suppl):209–18.

    PubMed  Google Scholar 

  • Peled AW, Slavin SA, Brorson H. Long-term outcome after surgical treatment of lipedema. Ann Plast Surg. 2012;68(3):303–7.

    PubMed  Google Scholar 

  • Pond CM, Mattacks CA. The source of fatty acids incorporated into proliferating lymphoid cells in immune-stimulated lymph nodes. Br J Nutr. 2003;89(3):375–83.

    PubMed  CAS  Google Scholar 

  • Petrova TV, Karpanen T, Norrmen C, Mellor R, Tamakoshi T, Finegold D, et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med. 2004;10(9):974–81.

    PubMed  CAS  Google Scholar 

  • Procaccini C, Jirillo E, Matarese G. Leptin as an immunomodulator. Mol Aspects Med. 2012;33(1):35–45.

    PubMed  CAS  Google Scholar 

  • Peyrin-Biroulet L, Chamaillard M, Gonzalez F, Beclin E, Decourcelle C, Antunes L, et al. Mesenteric fat in Crohn’s disease: a pathogenetic hallmark or an innocent bystander? Gut. 2007;56(4):577–83.

    PubMed  CAS  Google Scholar 

  • Pedica F, Ligorio C, Tonelli P, Bartolini S, Baccarini P. Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40. Virchows Arch. 2008;452(1):57–63.

    PubMed  CAS  Google Scholar 

  • Pandya NM, Dhalla NS, Santani DD. Angiogenesis–a new target for future therapy. Vascul Pharmacol. 2006;44(5):265–74.

    PubMed  CAS  Google Scholar 

  • Rehal S, Blanckaert P, Roizes S, von der Weid PY. Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels. Br J Pharmacol. 2009;158(8):1961–70.

    PubMed  CAS  Google Scholar 

  • Rutkowski JM, Boardman KC, Swartz MA. Characterization of lymphangiogenesis in a model of adult skin regeneration. Am J Physiol Heart Circ Physiol. 2006;291(3):H1402–10.

    PubMed  CAS  Google Scholar 

  • Rockson SG. Causes and consequences of lymphatic disease. Ann N Y Acad Sci. 2010;1207 Suppl 1:E2–6.

    PubMed  Google Scholar 

  • Ranallo RF, Rhodes EC. Lipid metabolism during exercise. Sports Med. 1998;26(1):29–42.

    PubMed  CAS  Google Scholar 

  • Rockson SG. Lymphedema. Am J Med. 2001;110(4):288–95.

    PubMed  CAS  Google Scholar 

  • Raica M, Cimpean AM, Ceausu R, Ribatti D. Lymphatic microvessel density, VEGF-C, and VEGFR-3 expression in different molecular types of breast cancer. Anticancer Res. 2011;31(5):1757–64.

    PubMed  CAS  Google Scholar 

  • Rupnick MA, Panigrahy D, Zhang CY, Dallabrida SM, Lowell BB, Langer R, et al. Adipose tissue mass can be regulated through the vasculature. Proc Natl Acad Sci U S A. 2002;99(16):10730–5.

    PubMed  CAS  Google Scholar 

  • Roberts N, Kloos B, Cassella M, Podgrabinska S, Persaud K, Wu Y, et al. Inhibition of VEGFR-3 activation with the antagonistic antibody more potently suppresses lymph node and distant metastases than inactivation of VEGFR-2. Cancer Res. 2006;66(5):2650–7.

    PubMed  CAS  Google Scholar 

  • Ribeiro R, Monteiro C, Cunha V, Oliveira MJ, Freitas M, Fraga A, et al. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro. J Exp Clin Cancer Res. 2012;31(1):32.

    PubMed  CAS  Google Scholar 

  • Ryan TJ. Lymphatics and adipose tissue. Clin Dermatol. 1995;13(5):493–8.

    PubMed  CAS  Google Scholar 

  • Ryan TJ. Structure and function of lymphatics. J Invest Dermatol. 1989;93(2 Suppl):18S–24.

    PubMed  CAS  Google Scholar 

  • Schulte-Merker S, Sabine A, Petrova TV. Lymphatic vascular morphogenesis in development, physiology, and disease. J Cell Biol. 2011;193(4):607–18.

    PubMed  CAS  Google Scholar 

  • Schmid-Schonbein GW. The second valve system in lymphatics. Lymphat Res Biol. 2003;1(1):25–9. discussion 9–31.

    PubMed  Google Scholar 

  • Shields JD. Lymphatics: at the interface of immunity, tolerance, and tumor metastasis. Microcirculation. 2011;18(7):517–31.

    PubMed  CAS  Google Scholar 

  • Skobe M, Detmar M. Structure, function, and molecular control of the skin lymphatic system. J Investig Dermatol Symp Proc. 2000;5(1):14–9.

    PubMed  CAS  Google Scholar 

  • Szuba A, Rockson SG. Lymphedema: classification, diagnosis and therapy. Vasc Med. 1998;3(2):145–56.

    PubMed  CAS  Google Scholar 

  • Shin WS, Szuba A, Rockson SG. Animal models for the study of lymphatic insufficiency. Lymphat Res Biol. 2003;1(2):159–69.

    PubMed  Google Scholar 

  • Schirger A, Harrison Jr EG, Janes JM. Idiopathic lymphedema. Review of 131 cases. JAMA. 1962;182:14–22.

    PubMed  CAS  Google Scholar 

  • Slavin SA, Van den Abbeele AD, Losken A, Swartz MA, Jain RK. Return of lymphatic function after flap transfer for acute lymphedema. Ann Surg. 1999;229(3):421–7.

    PubMed  CAS  Google Scholar 

  • Straub RH, Lowin T, Klatt S, Wolff C, Rauch L. Increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human synovium and mouse lymph nodes in arthritis. Arthritis Rheum. 2011;63(11):3234–42.

    PubMed  CAS  Google Scholar 

  • Suzuki-Inoue K, Fuller GL, Garcia A, Eble JA, Pohlmann S, Inoue O, et al. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood. 2006;107(2):542–9.

    PubMed  CAS  Google Scholar 

  • Schaffler A, Scholmerich J, Buchler C. Mechanisms of disease: adipocytokines and visceral adipose tissue–emerging role in intestinal and mesenteric diseases. Nat Clin Pract Gastroenterol Hepatol. 2005;2(2):103–11.

    PubMed  Google Scholar 

  • Silha JV, Krsek M, Sucharda P, Murphy LJ. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes (Lond). 2005;29(11):1308–14.

    CAS  Google Scholar 

  • Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001a;7(2):192–8.

    PubMed  CAS  Google Scholar 

  • Skobe M, Hamberg LM, Hawighorst T, Schirner M, Wolf GL, Alitalo K, et al. Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am J Pathol. 2001b;159(3):893–903.

    PubMed  CAS  Google Scholar 

  • Schoppmann SF, Fenzl A, Schindl M, Bachleitner-Hofmann T, Nagy K, Gnant M, et al. Hypoxia inducible factor-1alpha correlates with VEGF-C expression and lymphangiogenesis in breast cancer. Breast Cancer Res Treat. 2006;99(2):135–41.

    PubMed  CAS  Google Scholar 

  • Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med. 2001;7(2):186–91.

    PubMed  CAS  Google Scholar 

  • Tabibiazar R, Cheung L, Han J, Swanson J, Beilhack A, An A, et al. Inflammatory manifestations of experimental lymphatic insufficiency. PLoS Med. 2006;3(7):e254.

    PubMed  Google Scholar 

  • Tanaka H, Zaima N, Sasaki T, Yamamoto N, Sano M, Konno H, et al. Loss of lymphatic vessels and regional lipid accumulation is associated with great saphenous vein incompetence. J Vasc Surg. 2012;55(5):1440–8.

    PubMed  Google Scholar 

  • Tso P, Pitts V, Granger DN. Role of lymph flow in intestinal chylomicron transport. Am J Physiol. 1985;249(1 Pt 1):G21–8.

    PubMed  CAS  Google Scholar 

  • Tammela T, Petrova TV, Alitalo K. Molecular lymphangiogenesis: new players. Trends Cell Biol. 2005a;15(8):434–41.

    PubMed  CAS  Google Scholar 

  • Tammela T, Saaristo A, Lohela M, Morisada T, Tornberg J, Norrmen C, et al. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood. 2005b;105(12):4642–8.

    PubMed  CAS  Google Scholar 

  • Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2004;92(3):347–55.

    PubMed  CAS  Google Scholar 

  • Unna P. The histopathology of the disease of the skin. New York: Macmillan; 1896.

    Google Scholar 

  • Voros G, Maquoi E, Demeulemeester D, Clerx N, Collen D, Lijnen HR. Modulation of angiogenesis during adipose tissue development in murine models of obesity. Endocrinology. 2005;146(10):4545–54.

    PubMed  CAS  Google Scholar 

  • von der Weid PY, Van Helden DF. Beta-adrenoceptor-mediated hyperpolarization in lymphatic smooth muscle of guinea pig mesentery. Am J Physiol. 1996;270(5 Pt 2):H1687–95.

    PubMed  Google Scholar 

  • Wang B, Wood IS, Trayhurn P. Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. Pflugers Arch. 2007;455(3):479–92.

    PubMed  CAS  Google Scholar 

  • Wang L, Gill R, Pedersen TL, Higgins LJ, Newman JW, Rutledge JC. Triglyceride-rich lipoprotein lipolysis releases neutral and oxidized FFAs that induce endothelial cell inflammation. J Lipid Res. 2009a;50(2):204–13.

    PubMed  CAS  Google Scholar 

  • Wong L, Sivok B, Kurucz E, Sloop CH, Roheim PS, Asztalos B. Lipid composition of HDL subfractions in dog plasma and lymph. Arterioscler Thromb Vasc Biol. 1995;15(11):1875–81.

    PubMed  CAS  Google Scholar 

  • Wang W, von der Weid PY, Muthuchamy M, Zawieja DC. Low density lipoprotein modulates rat mesenteric lymphatic pumping. Microcirculation. 2009b;16:766.

    Google Scholar 

  • Westcott E, Windsor A, Mattacks C, Pond C, Knight S. Fatty acid compositions of lipids in mesenteric adipose tissue and lymphoid cells in patients with and without Crohn’s disease and their therapeutic implications. Inflamm Bowel Dis. 2005;11(9):820–7.

    PubMed  Google Scholar 

  • Wigle JT, Oliver G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999;98(6):769–78.

    PubMed  CAS  Google Scholar 

  • Weatherill AR, Lee JY, Zhao L, Lemay DG, Youn HS, Hwang DH. Saturated and polyunsaturated fatty acids reciprocally modulate dendritic cell functions mediated through TLR4. J Immunol. 2005;174(9):5390–7.

    PubMed  CAS  Google Scholar 

  • Wiley HE, Gonzalez EB, Maki W, Wu MT, Hwang ST. Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma. J Natl Cancer Inst. 2001;93(21):1638–43.

    PubMed  CAS  Google Scholar 

  • Wang YY, Lehuede C, Laurent V, Dirat B, Dauvillier S, Bochet L, et al. Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer. Cancer Lett. 2012;324(2):142–51.

    PubMed  CAS  Google Scholar 

  • Wagner M, Bjerkvig R, Wiig H, Melero-Martin JM, Lin RZ, Klagsbrun M, et al. Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis. Angiogenesis. 2012;15(3):481–95.

    PubMed  CAS  Google Scholar 

  • Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, et al. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 2002;21(7):1505–13.

    PubMed  CAS  Google Scholar 

  • Wada H, Ura S, Kitaoka S, Satoh-Asahara N, Horie T, Ono K, et al. Distinct characteristics of circulating vascular endothelial growth factor-a and C levels in human subjects. PLoS One. 2011;6(12):e29351.

    PubMed  CAS  Google Scholar 

  • Xue Y, Petrovic N, Cao R, Larsson O, Lim S, Chen S, et al. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab. 2009;9(1):99–109.

    PubMed  CAS  Google Scholar 

  • Yuan L, Moyon D, Pardanaud L, Breant C, Karkkainen MJ, Alitalo K, et al. Abnormal lymphatic vessel development in neuropilin 2 mutant mice. Development. 2002;129(20):4797–806.

    PubMed  CAS  Google Scholar 

  • Yoffey JM, Drinker CK. The lymphatic pathway from the nose and pharynx : the absorption of dyes. J Exp Med. 1938;68(4):629–40.

    PubMed  CAS  Google Scholar 

  • Yoffey JM, Sullivan ER, Drinker CK. The lymphatic pathway from the nose and pharynx : the absorption of certain proteins. J Exp Med. 1938;68(6):941–7.

    PubMed  CAS  Google Scholar 

  • Yan A, Avraham T, Zampell JC, Haviv YS, Weitman E, Mehrara BJ. Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-beta1 inhibition. Future Oncol. 2011;7(12):1457–73.

    PubMed  CAS  Google Scholar 

  • Yoon M, Kim MY. The anti-angiogenic herbal composition Ob-X from Morus alba, Melissa officinalis, and Artemisia capillaris regulates obesity in genetically obese ob/ob mice. Pharm Biol. 2011;49(6):614–9.

    PubMed  Google Scholar 

  • Zampell JC, Aschen S, Weitman ES, Yan A, Elhadad S, De Brot M, et al. Regulation of adipogenesis by lymphatic fluid stasis: part I. Adipogenesis, fibrosis, and inflammation. Plast Reconstr Surg. 2012;129(4):825–34.

    PubMed  CAS  Google Scholar 

  • Zawieja SD, Wang W, Wu X, Nepiyushchikh ZV, Zawieja DC, Muthuchamy M. Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome. Am J Physiol Heart Circ Physiol. 2012;302(3):H643–53.

    PubMed  CAS  Google Scholar 

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    1. Department of Physiology & Pharmacology, Inflammation Research Network and Smooth Muscle Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 3330 Hospital Drive N.W., Calgary, AB, Canada, T2N 4N1

      Bernhard Nausch Ph.D., Sonia Rehal M.Sc. & Pierre-Yves von der Weid

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    2. Sonia Rehal M.Sc.
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    3. Pierre-Yves von der Weid
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    Correspondence to Pierre-Yves von der Weid .

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      Yihai Cao

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    Nausch, B., Rehal, S., von der Weid, PY. (2013). Lymphatic System in Adipose Tissues. In: Cao, Y. (eds) Angiogenesis in Adipose Tissue. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8069-3_6

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