Exercise training improves obesity‐related lymphatic dysfunction

Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells.

[1]  B. Mehrara,et al.  Lymphatic function regulates contact hypersensitivity dermatitis in obesity , 2015, The Journal of investigative dermatology.

[2]  M. Hill,et al.  Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling. , 2015, Cardiovascular research.

[3]  B. Mehrara,et al.  Th2 Cytokines Inhibit Lymphangiogenesis , 2015, PloS one.

[4]  M. Nussenzweig,et al.  Collecting Lymphatic Vessel Permeability Facilitates Adipose Tissue Inflammation and Distribution of Antigen to Lymph Node–Homing Adipose Tissue Dendritic Cells , 2015, The Journal of Immunology.

[5]  Young-Kwon Hong,et al.  TH2 cells and their cytokines regulate formation and function of lymphatic vessels , 2015, Nature Communications.

[6]  K. Alitalo,et al.  Blockade of VEGF-C and VEGF-D modulates adipose tissue inflammation and improves metabolic parameters under high-fat diet , 2014, Molecular metabolism.

[7]  D. Fearon,et al.  Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8+ T cells , 2014, Proceedings of the National Academy of Sciences.

[8]  K. Alitalo,et al.  Lymphatic Vessel Insufficiency in Hypercholesterolemic Mice Alters Lipoprotein Levels and Promotes Atherogenesis , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[9]  G. Steinberg,et al.  Endurance interval training in obese mice reduces muscle inflammation and macrophage content independently of weight loss , 2014, Physiological reports.

[10]  T. Petrova,et al.  Pressing the right buttons: signaling in lymphangiogenesis. , 2014, Blood.

[11]  M. Detmar,et al.  Chronic High-Fat Diet Impairs Collecting Lymphatic Vessel Function in Mice , 2014, PloS one.

[12]  D. Zawieja,et al.  The effects of inflammatory cytokines on lymphatic endothelial barrier function , 2014, Angiogenesis.

[13]  G. Randolph,et al.  Lymphatic transport of high-density lipoproteins and chylomicrons. , 2014, The Journal of clinical investigation.

[14]  Yoshiki Tokura,et al.  Potential application of in vivo imaging of impaired lymphatic duct to evaluate the severity of pressure ulcer in mouse model , 2014, Scientific Reports.

[15]  Haiming Cao Adipocytokines in obesity and metabolic disease. , 2014, The Journal of endocrinology.

[16]  E. Sevick-Muraca,et al.  Cytokines are systemic effectors of lymphatic function in acute inflammation. , 2013, Cytokine.

[17]  B. Mehrara,et al.  Obesity Impairs Lymphatic Fluid Transport and Dendritic Cell Migration to Lymph Nodes , 2013, PloS one.

[18]  H. Kidoya,et al.  Apelin Inhibits Diet-Induced Obesity by Enhancing Lymphatic and Blood Vessel Integrity , 2013, Diabetes.

[19]  J. Holst,et al.  Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: a possible link between obesity and local tissue inflammation? , 2013, International Journal of Obesity.

[20]  J. Woods,et al.  Exercise Training Effects on Inflammatory Gene Expression in White Adipose Tissue of Young Mice , 2012, Mediators of inflammation.

[21]  B. Mehrara,et al.  CD4+ Cells Regulate Fibrosis and Lymphangiogenesis in Response to Lymphatic Fluid Stasis , 2012, PloS one.

[22]  K. Alitalo,et al.  Impaired Humoral Immunity and Tolerance in K14-VEGFR-3-Ig Mice That Lack Dermal Lymphatic Drainage , 2012, The Journal of Immunology.

[23]  A. Gashev,et al.  Evidence of increased oxidative stress in aged mesenteric lymphatic vessels. , 2012, Lymphatic research and biology.

[24]  Frederick D. Grant,et al.  Lower-extremity lymphedema and elevated body-mass index. , 2012, The New England journal of medicine.

[25]  D. Zawieja,et al.  Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome. , 2012, American journal of physiology. Heart and circulatory physiology.

[26]  B. Mehrara,et al.  Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines. , 2012, American journal of physiology. Cell physiology.

[27]  E. Kremmer,et al.  Lymph node T cell homeostasis relies on steady state homing of dendritic cells. , 2011, Immunity.

[28]  Dai Fukumura,et al.  Impaired lymphatic contraction associated with immunosuppression , 2011, Proceedings of the National Academy of Sciences.

[29]  C. Halin,et al.  Tissue inflammation modulates gene expression of lymphatic endothelial cells and dendritic cell migration in a stimulus-dependent manner. , 2011, Blood.

[30]  G. Koh,et al.  T lymphocytes negatively regulate lymph node lymphatic vessel formation. , 2011, Immunity.

[31]  D. Jackson,et al.  Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration. , 2010, International immunology.

[32]  Quan Zhou,et al.  Near-infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute versus chronic phases of arthritis in mice. , 2010, Arthritis and rheumatism.

[33]  E. Mervaala,et al.  Periadventitial adipose tissue promotes endothelial dysfunction via oxidative stress in diet-induced obese C57Bl/6 mice. , 2010, Circulation journal : official journal of the Japanese Circulation Society.

[34]  Melody A. Swartz,et al.  Fluid Flow Regulates Stromal Cell Organization and CCL21 Expression in a Tissue-Engineered Lymph Node Microenvironment1 , 2009, The Journal of Immunology.

[35]  Sai T Reddy,et al.  Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. , 2009, The American journal of pathology.

[36]  T. Kadowaki,et al.  CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity , 2009, Nature Medicine.

[37]  J. Lawler,et al.  Exercise training modulates the nitric oxide synthase profile in skeletal muscle from old rats. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[38]  J. Holloszy,et al.  Effects of exercise on glucose tolerance and insulin resistance. Brief review and some preliminary results. , 2009, Acta medica Scandinavica. Supplementum.

[39]  A. Heagerty,et al.  Local Inflammation and Hypoxia Abolish the Protective Anticontractile Properties of Perivascular Fat in Obese Patients , 2009, Circulation.

[40]  J. Jeon,et al.  Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice. , 2008, American journal of physiology. Endocrinology and metabolism.

[41]  R. Yu,et al.  Visceral Fat Accumulation Induced by a High‐fat Diet Causes the Atrophy of Mesenteric Lymph Nodes in Obese Mice , 2008, Obesity.

[42]  Hiroshi I. Suzuki,et al.  Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis. , 2008, Blood.

[43]  Mardge H. Cohen,et al.  Obesity and immune cell counts in women. , 2007, Metabolism: clinical and experimental.

[44]  J. Helge,et al.  Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. , 2006, American journal of physiology. Endocrinology and metabolism.

[45]  Guillermo Oliver,et al.  Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity , 2005, Nature Genetics.

[46]  M. Kaneki,et al.  Inducible Nitric-oxide Synthase and NO Donor Induce Insulin Receptor Substrate-1 Degradation in Skeletal Muscle Cells* , 2005, Journal of Biological Chemistry.

[47]  E. Fisher,et al.  Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. , 2004, Immunity.

[48]  T. Blankenstein,et al.  CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. , 2004, Immunity.

[49]  F. Aktan iNOS-mediated nitric oxide production and its regulation. , 2004, Life sciences.

[50]  Antonio Lanzavecchia,et al.  Regulation of Dendritic Cell Migration to the Draining Lymph Node , 2003, The Journal of experimental medicine.

[51]  M. Detmar,et al.  An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype , 2002, The EMBO journal.

[52]  A. Marette,et al.  Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle , 2001, Nature Medicine.

[53]  E. Wolf,et al.  CCR7 Coordinates the Primary Immune Response by Establishing Functional Microenvironments in Secondary Lymphoid Organs , 1999, Cell.

[54]  A. Utter,et al.  Influence of obesity on immune function. , 1999, Journal of the American Dietetic Association.

[55]  K. Alitalo,et al.  Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. , 1998, Science.

[56]  J. Cyster,et al.  A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Per Capita,et al.  About the authors , 1995, Machine Vision and Applications.

[58]  M. Nussenzweig,et al.  Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue DCs , 2015 .

[59]  J. Daly Blockade of Transforming Growth Factor-β1 Accelerates Lymphatic Regeneration During Wound Repair , 2011 .

[60]  L. Helyer,et al.  Obesity is a Risk Factor for Developing Postoperative Lymphedema in Breast Cancer Patients , 2010, The breast journal.

[61]  B. Mehrara,et al.  TGF- (cid:1) 1 is a negative regulator of lymphatic regeneration during wound repair , 2008 .