Advertisement

Adipose tissue and the immune system

      Abstract

      Adipocytes anatomically associated with lymph nodes (and omental milky spots) have many special properties including fatty acid composition and the control of lipolysis that equip them to interact locally with lymphoid cells. Lymph node lymphocytes and tissue dendritic cells acquire their fatty acids from the contiguous adipocytes. Lymph node-derived dendritic cells suppress lipolysis in perinodal adipocytes but those that permeate the adipose tissue stimulate lipolysis, especially after minor, local immune stimulation. Inflammation alters the composition of fatty acids incorporated into dendritic cells, and that of node-containing adipose tissue, counteracting the effects of dietary lipids. Thus these specialised adipocytes partially emancipate the immune system from fluctuations in the abundance and composition of dietary lipids.
      Prolonged, low-level immune stimulation induces the local formation of more adipocytes, especially adjacent to the inflamed lymph node. This mechanism may contribute to hypertrophy of the mesentery and omentum in chronic inflammatory diseases such as HIV-infection, and in smokers. Paracrine interactions between adipose and lymphoid tissues are enhanced by diets rich in n-6 fatty acids and attentuated by fish oils. The latter improve immune function and body conformation in animals and people. The partitioning of adipose tissue in many depots, some specialised for local, paracrine interactions with other tissues, is a fundamental feature of mammals.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Prostaglandins, Leukotrienes and Essential Fatty Acids
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Rosen B.S.
        • Cook K.S.
        • Yaglom J.
        • Groves D.L.
        • Volanakis J.E.
        • Damn D.
        • White T.
        • Spiegelman B.M.
        Adipsin and complement factor D activity: an immune-related defect in obesity.
        Science. 1989; 244: 1483-1487
        • Choy L.N.
        • Rosen B.S.
        • Spiegelman B.M.
        Adipsin and endogenous pathway of complement from adipose cells.
        J. Biol. Chem. 1992; 267: 12,736-127,541
        • Cook K.S.
        • Min H.Y.
        • Johnson D.
        • Chupliusky R.J.
        • Flier J.S.
        • Hunt C.R.
        • Spiegelman B.M.
        Adipsin: a circulating semi protease homologue secreted by adipose tissue and sciatic nerve.
        Science. 1987; 237: 402-495
        • Coppack S.W.
        Pro-inflammatory cytokines and adipose tissue.
        Proc. Nutr. Soc. 2001; 60: 349-356
        • Lord G.M.
        • Matarese G.
        • Howard J.K.
        • Baker R.J.
        • Bloom S.R.
        • Lechler R.I.
        Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression.
        Nature (London). 1998; 394: 897-901
        • La Cava A.
        • Matarese G.
        The weight of leptin in immunity.
        Nat. Rev. Immunol. 2004; 4: 371-379
        • Matarese G.
        • La Cava A.
        The intricate interface between immune system and metabolism.
        Trends Immunol. 2004; 25: 193-200
        • Chehab F.F.
        • Qiu J.
        • Ogus S.
        The use of animal models to dissect the biology of leptin.
        Rec. Progr. Horm. Res. 2004; 59: 245-266
        • Zhang H.H.
        • Kumar S.
        • Barnett A.H.
        • Eggo M.C.
        Intrinsic site-specific differences in the expression of leptin in human adipocytes and its autocrine effects on glucose uptake.
        J. Clin. Endocrinol. Metab. 1999; 84: 2550-2556
        • Schoof E.
        • Stuppy A.
        • Harig F.
        • Carbon R.
        • Horbach T.
        • Stohr W.
        • Rascher W.
        • Dotsch J.
        Comparison of leptin gene expression in different adipose tissues in children.
        Eur. J. Endocrinol. 2004; 150: 579-584
        • Montague C.T.
        • Prins J.B.
        • Sanders L.
        • Digby J.E.
        • Orahilly S.
        Depot- and sex-specific differences in human leptin mRNA expression—implications for the control of regional fat distribution.
        Diabetes. 1997; 46: 342-347
        • Hube F.
        • Lietz U.
        • Igel M.
        • Jensen P.B.
        • Tornqvist H.
        • Joost H.G.
        • Hauner H.
        Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans.
        Horm. Metab. Res. 1996; 28: 690-693
        • Trayhurn P.
        Biology of leptin—its implications and consequences for the treatment of obesity.
        Int. J. Obes. 2001; 25: S26-S28
        • Laharrague P.
        • Larrouy D.
        • Fontanilles A.M.
        • Truel N.
        • Campfield A.
        • Tenenbaum R.
        • Galitzky J.
        • Corberand J.X.
        • Penicaud L.
        • Casteilla L.
        High expression of leptin by human bone marrow adipocytes in primary culture.
        FASEB J. 1998; 12: 747-752
        • Morroni M.
        • De Matteis R.
        • Palumbo C.
        • Ferretti M.
        • Villa I.
        • Rubinacci A.
        • Cinti S.
        • Marotti G.
        In vivo leptin expression in cartilage and bone cells of growing rats and adult humans.
        J. Anat. 2004; 205: 291-296
        • Hamrick M.W.
        • Pennington C.
        • Newton D.
        • Xie D.
        • Isales C.
        Leptin deficiency produces contrasting phenotypes in bones of the limb and spine.
        Bone. 2004; 34: 376-383
        • Thomas T.
        • Gori F.
        • Khosla S.
        • Jensen M.D.
        • Burguera B.
        • Riggs B L.
        Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes.
        Endocrinology. 1999; 140: 1630-1638
        • Jensen M.D.
        • Moller N.
        • Nair K.S.
        • Eisenberg P.
        • Landt M.
        • Klein S.
        Regional leptin kinetics in humans.
        Am. J. Clin. Nutr. 1999; 69: 18-21
        • Gyllensten L.
        The postnatal histogenesis of the lymphatic system of guinea-pigs.
        Acta Anat. 1950; 10: 130-160
        • Crivellato E.
        • Vacca A.
        • Ribatti D.
        Setting the stage: an anatomist's view of the immune system.
        Trends Immunol. 2004; 25: 210-217
        • Kim D.
        • Mebius R.E.
        • MacMicking J.D.
        • Jung S.
        • Cupedo T.
        • Castellanos Y.
        • Rho J.
        • Wong .
        • Josien R.
        • Kim N.
        • Rennert P.D.
        • Choi Y.
        Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE.
        J. Exp. Med. 2000; 192: 1467-1478
        • Kim C.
        • Li B.
        • Papaiconomou C.
        • Zakharov A.
        • Johnston M.
        Functional impact of lymphangiogenesis on fluid transport after lymph node excision.
        Lymphology. 2003; 36: 111-119
        • Ikomi F.
        • Zweifach B.W.
        • Schmid-Schonbein G.W.
        Fluid pressures in the rabbit popliteal afferent lymphatics during passive tissue motion.
        Lymphology. 1997; 30: 113-123
        • Heath T.
        • Brandon R.
        Lymphatic and blood vessels of the popliteal node in sheep.
        Anat. Rec. 1983; 207: 461-472
        • Shields J.W.
        Lymph, lymph glands, and homeostasis.
        Lymphology. 1992; 25: 147-153
        • Shimotsuma M.
        • Shields J.W.
        • Simpson-Morgan M.W.
        • Sakuyama A.
        • Shirasu M.
        • Hagiwara A.
        • Takahashi T.
        Morpho-physiological function and role of omental milky spots as omentum-associated lymphoid tissue (OALT) in the peritoneal cavity.
        Lymphology. 1993; 26: 90-101
        • van Vugt E.
        • van Rijthoven E.A.M.
        • Kamperdijk E.W.A.
        • Beelen R.H.J.
        Omental milky spots in the local immune response in the peritoneal cavity of rats.
        Anat. Rec. 1996; 244: 235-245
        • Matarese G.
        • La Cava A.
        • Sanna V.
        • Lord G.M.
        • Lechler R.I.
        • Fontana S.
        • Zappacosta S.
        Balancing susceptibility to infection and autoimmunity: a role for leptin?.
        Trends Immunol. 2002; 23: 182-187
        • Misra A.
        • Vikram N.K.
        Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots.
        Nutrition. 2003; 19: 457-466
        • Crandall D.L.
        • Goldstein B.M.
        • Huggins F.
        • Cervoni P.
        Adipocyte blood flow: influence of age, anatomic location and dietary manipulation.
        Am. J. Physiol. 1984; 247: R46-51
        • Pond C.M.
        The Fats of Life.
        Cambridge University Press, Cambridge1998
        • Sjöström L.
        • Björntorp P.
        Body composition and adipose tissue cellularity in human obesity.
        Acta Med. Scand. 1974; 195: 201-211
        • Pond C.M.
        • Mattacks C.A.
        Body mass and natural diet as determinants of the number and volume of adipocytes in eutherian mammals.
        J. Morphol. 1985; 185: 183-193
        • Mattacks C.A.
        • Sadler D.
        • Pond C.M.
        The cellular structure and lipid/protein composition of adipose tissue surrounding chronically stimulated lymph nodes in rats.
        J. Anat. (London). 2003; 202: 551-561
        • Mattacks C.A.
        • Pond C.M.
        Interactions of noradrenalin and tumour necrosis factor-a, interleukin-4 and interleukin-6 in the control of lipolysis from adipocytes around lymph nodes.
        Cytokine. 1999; 11: 334-346
        • MacQueen H.A.
        • Pond C.M.
        Immunofluorescent localisation of tumour necrosis factor-a receptors on the popliteal lymph node and the surrounding adipose tissue following a simulated immune challenge.
        J. Anat. (London). 1998; 192: 223-231
        • Huang F-.P.
        • Platt N.
        • Wykes M.
        • Major J.R.
        • Powell T.J.
        • Jenkins C.D.
        • MacPherson G.G.
        A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes.
        J. Exp. Med. 2000; 191: 435-443
        • Xu H.Y.
        • Barnes G.T.
        • Yang Q.
        • Tan Q.
        • Yang D.S.
        • Chou C.J.
        • Sole J.
        • Nichols A.
        • Ross J.S.
        • Tartaglia L.A.
        • Chen H.
        Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
        J. Clin. Invest. 2003; 112: 1821-1830
        • Mattacks C.A.
        • Sadler D.
        • Pond C.M.
        The effects of dietary lipids on dendritic cells in perinodal adipose tissue during chronic mild inflammation.
        Br. J. Nutr. 2004; 91: 883-891
        • Mowat A.M.
        • Viney J.L.
        The anatomical basis of intestinal immunity.
        Immunol. Rev. 1997; 156: 145-166
        • Smith J.B.
        • Morris B.
        The response of the popliteal lymph node of the sheep to swine influenza virus.
        Aust. J. Exp. Biol. Med. 1970; 48: 47-55
        • Mattacks C.A.
        • Pond C.M.
        The effects of feeding suet-enriched chow on site-specific differences in the composition of triacylglycerol fatty acids in adipose tissue and its interactions in vitro with lymphoid cells.
        Br. J. Nutr. 1997; 77: 621-643
        • Mattacks C.A.
        • Sadler D.
        • Pond C.M.
        Site-specific differences in the fatty acid compositions of dendritic cells and associated adipose tissue in popliteal depot, mesentery and omentum, and their modulation by chronic inflammation and dietary lipids.
        Lymph Res. Biol. 2004; 2: 107-129
        • Bagga D.
        • Wang L.
        • Farias-Eisner R.
        • Glaspy J.A.
        • Reddy S.T.
        Differential effects of prostaglandin derived from w-6 and w-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion.
        Proc. Natl. Acad. Sci. USA. 2003; 100: 1751-1756
        • Serhan C.N.
        • Hong S.
        • Gronert K.
        • Colgan S.P.
        • Devchand P.R.
        • Mirick G.
        • Moussignac R.L.
        Resolvins: A family of bioactive products of w-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals.
        J. Exp. Med. 2002; 196: 1025-1037
        • Pond C.M.
        • Mattacks C.A.
        The source of fatty acids incorporated into proliferating lymphoid cells in immune-stimulated lymph nodes.
        Br. J. Nutr. 2003; 89: 375-382
        • Cooke C.J.
        • Nanjee M.N.
        • Stepanova I.P.
        • Olszewski W.L.
        • Miller N.E.
        Variations in lipid and apolipoprotein concentrations in human leg lymph: effects of posture and physical exercise.
        Atherosclerosis. 2004; 173: 39-45
        • Morelli A.E.
        • Thomson A.W.
        Dendritic cells under the spell of prostaglandins.
        Trends Immunol. 2003; 24: 108-111
        • Raclot T.
        Selective mobilization of fatty acids from adipose tissue triacylglycerols.
        Progr. Lipid Res. 2003; 42: 257-288
        • Raclot T.
        • Holm C.
        • Langin D.
        Fatty acid specificity of hormone-sensitive lipase: implication in the selective hydrolysis of triacylglycerols.
        J. Lipid Res. 2001; 42: 2049-2057
        • Pond C.M.
        • Mattacks C.A.
        In vivo evidence for the involvement of the adipose tissue surrounding lymph nodes in immune responses.
        Immunol. Lett. 1998; 63: 159-167
        • Pond C.M.
        • Mattacks C.A.
        The activation of adipose tissue associated with lymph nodes during the early stages of an immune response.
        Cytokine. 2002; 17: 131-139
        • Mattacks C.A.
        • Sadler D.
        • Pond C.M.
        The effects of dietary lipids on adrenergically stimulated lipolysis in perinodal adipose tissue following prolonged activation of a single lymph node.
        Br. J. Nutr. 2002; 87: 375-382
        • MacQueen H.A.
        • Sadler D.
        • Mattacks C.A.
        Dietary fatty acids influence the appearance of tumour necrosis factor-a receptors on adipocytes following an immune challenge.
        Br. J. Nutr. 2000; 84: 387-392
        • Mattacks C.A.
        • Sadler D.
        • Pond C.M.
        The control of lipolysis in perinodal and other adipocytes by lymph node and adipose tissue-derived dendritic cells in rats.
        Adipocytes. 2005; 1: 43-56
        • Mempel T.R.
        • Henrickson S.E.
        • von Andrian U.
        T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases.
        Nature. 2004; 427: 154-159
        • Pond C.M.
        Paracrine interactions of mammalian adipose tissue.
        J. Exp. Zool. 2003; 295A: 99-110
        • Dykstra M.
        • Cherukuri A.
        • Sohn H.W.
        • Tzeng S.J.
        • Pierce S.K.
        Location is everything: lipid rafts and immune cell signaling.
        Annu. Rev. Immunol. 2003; 21: 457-481
        • Pizzo P.
        • Viola A.
        Lymphocyte lipid rafts: structure and function.
        Curr. Opin. Immunol. 2003; 15: 255-260
        • Cohen A.W.
        • Combs T.P.
        • Scherer P.E.
        • Lisanti M.P.
        Role of caveolin and caveolae in insulin signaling and diabetes.
        Am. J. Physiol.–Endocrinol. Metab. 2003; 285: E1151-E1160
        • Lee J.Y.
        • Plakidas A.
        • Lee W.H.
        • Heikkinen A.
        • Chanmugam P.
        • Bray G.
        • Hwang D.H.
        Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids.
        J. Lipid Res. 2003; 44: 479-486
        • Jump D.B.
        Fatty acid regulation of gene transcription.
        Crit. Rev. Clin. Lab. Sci. 2004; 41: 41-78
        • Balazy M.
        Eicosanomics: targeted lipidomics of eicosanoids in biological systems.
        Prostaglandins Other Lipid Mediat. 2004; 73: 173-180
        • Ivanova P.T.
        • Milne S.B.
        • Forrester J.S.
        • Brown H.A.
        Lipid arrays: new tools in the understanding of membrane dynamics and lipid signaling.
        Mol. Interv. 2004; 4: 86-96
        • Stulnig T.M.
        Immunomodulation by polyunsaturated fatty acids: mechanisms and effects.
        Int. Arch. Allergy Immunol. 2003; 132: 310-321
        • Calder P.C.
        Dietary modification of inflammation with lipids.
        Proc. Nutr. Soc. 2002; 61: 345-358
        • Hausman D.B.
        • DiGirolamo M.
        • Bartness T.J.
        • Hausman G.J.
        • Martin R J.
        The biology of white adipocyte proliferation.
        Obes. Rev. 2001; 2: 239-254
        • Fukumura D.
        • Ushiyama A.
        • Duda D G.
        • Xu L.
        • Tam J.
        • Chatterjee V.K.K.
        • Garkavtsev I.
        • Jain R.K.
        Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis.
        Circ. Res. 2003; 93: E88-E97
        • Rupnick M.
        • Panigrahy D.
        • Zhang C.
        • Dallabrida S.
        • Lowell B.
        • Langer R.
        • Folkman M.
        Adipose tissue mass can be regulated through the vasculature.
        Proc. Natl. Acad. Sci. USA. 2002; 99: 10,730-10,735
        • Rosen E.D.
        The molecular control of adipogenesis, with special reference to lymphatic pathology.
        Ann. NY Acad. Sci. 2002; 979: 143-158
        • Pond C.M.
        Long-term changes in adipose tissue in human disease.
        Proc. Nutr. Soc. 2001; 60: 365-374
        • Rockson S.G.
        The elusive adipose connection.
        Lymph Res. Biol. 2004; 2: 105-106
        • Grewal S.S.
        • Edgar B.A.
        Controlling cell division in yeast and animals: does size matter?.
        J. Biol. 2003; 2: 5
        • Pond C.M.
        • Mattacks C.A.
        • Colby R.H.
        • Tyler N.J.C.
        The anatomy, chemical composition and maximum glycolytic capacity of adipose tissue in wild Svalbard reindeer (Rangifer tarandus platyrhynchus) in winter.
        J. Zool. (London). 1993; 229: 17-40
        • Unger R.H.
        Lipid overload and overflow: metabolic trauma and the metabolic syndrome.
        Trends Endocrinol. Metab. 2003; 14: 398-403
        • Orci L.
        • Cook W.S.
        • Ravazzola M.
        • Wang M.Y.
        • Park B.H.
        • Montesano R.
        • Unger R.H.
        Rapid transformation of white adipocytes into fat-oxidizing machines.
        Proc. Natl. Acad. Sci. USA. 2004; 101: 2058-2063
        • Dhurandhar N.V.
        • Israel B.A.
        • Kolesar J.M.
        • Mayhew G.F.
        • Cook M.E.
        • Atkinson R.L.
        Increased adiposity in animals due to a human virus.
        Int. J. Obesity. 2000; 24: 989-996
        • Dhurandhar N.V.
        Contribution of pathogens in human obesity.
        Drug News Perspect. 2004; 17: 307-313
        • Pond C.M.
        • Mattacks C.A.
        • Colby R.H.
        • Ramsay M.A.
        The anatomy, chemical composition and metabolism of adipose tissue in wild polar bears (Ursus maritimus).
        Can. J. Zool. 1992; 70: 326-341
        • Pond C.M.
        • Mattacks C.A.
        • Prestrud P.
        Variability in the distribution and composition of adipose tissue in arctic foxes (Alopex lagopus) on Svalbard.
        J. Zool. (London). 1995; 236: 593-610
        • Pond C.M.
        • Mattacks C.A.
        The anatomy of adipose tissue in captive Macaca monkeys and its implications for human biology.
        Folia Primatol. 1987; 48: 164-185
        • Pereira M.E.
        • Pond C.M.
        Organization of white adipose tissue in lemuridae.
        Am. J. Primatol. 1995; 35: 1-13
        • Jones P.R.M.
        • Edwards D.A.
        Areas of fat loss in overweight young females following an 8-week period of energy intake reduction.
        Ann. Hum. Biol. 1999; 26: 151-162
        • Seidell J.C.
        • Cigolini M.
        • Deslypere J-.P.
        • Charzewska J.
        • Ellsinger B-.M.
        • Cruz A.
        Body-fat distribution in relation to physical activity and smoking habits in 38-year-old European men. The European fat distribution study.
        Am. J. Epidemiol. 1991; 133: 257-265
        • Singh D.
        • Young R.K.
        Body weight, waist-to-hip ratio, breasts, and hips: Role in judgments of female attractiveness and desirability for relationships.
        Ethol. Sociobiol. 1995; 16: 483-507
        • Björntorp P.
        The regulation of adipose-tissue distribution in humans.
        Int. J. Obesity. 1996; 20: 291-302
        • Singh D.
        Adaptive significance of female physical attractiveness: the role of waist-to-hip ratio.
        J. Personal Soc. Psychol. 1993; 654: 293-307
        • Frayn K.N.
        Visceral fat and insulin resistance—causative or correlative?.
        Br. J. Nutr. 2000; 83: S71-S77
        • Grimble R.F.
        Inflammatory status and insulin resistance.
        Curr. Opin. Clin. Nutr. Metab. Care. 2002; 5: 551-559
        • Dandona P.
        • Aljada A.
        • Bandyopadhyay A.
        Inflammation: the link between insulin resistance, obesity and diabetes.
        Trends Immunol. 2004; 25: 4-7
        • Fain J.N.
        • Bahouth S.W.
        • Madan A.K.
        TNFa release by the nonfat cells of human adipose tissue.
        Int. J. Obes. 2004; 28: 616-622
        • Lin E.
        • Kotani J.G.
        • Lowry S.F.
        Nutritional modulation of immunity and inflammatory response.
        Nutrition. 1998; 14: 545-550
        • Lochmiller R.L.
        • Deerenberg C.
        Trade-offs in evolutionary immunology: just what is the cost of immunity?.
        Oikos. 2000; 88: 87-99
        • Pedersen B.K.
        Exercise and cytokines.
        Immunol. Cell Biol. 2000; 78: 532-535
        • Nova E.
        • Samartin S.
        • Gomez S.
        • Morande G.
        • Marcos A.
        The adaptive response of the immune system to the particular malnutrition of eating disorders.
        Eur. J. Clin. Nutr. 2002; 56: S34-S37
        • Birmingham C.L.
        • Hodgson D.M.
        • Fung J.
        • Brown R.
        • Wakefield A.
        • Bartrop R.
        • Beumont P.
        Reduced febrile response to bacterial infection in anorexia nervosa patients.
        Int. J. Eating Disord. 2003; 34: 269-272
        • Brichard S.M.
        • Delporte M.L.
        • Lambert M.
        Adipocytokines in anorexia nervosa: a review focusing on leptin and adiponectin.
        Horm. Metab. Res. 2003; 35: 337-342
        • Dixit V.D.
        • Schaffer E.M.
        • Pyle R.S.
        • Collins G.D.
        • Sakthivel S.K.
        • Palaniappan R.
        • Lillard J.W.
        • Taub D.D.
        Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.
        J. Clin. Invest. 2004; 114: 57-66
        • Haskó G.
        • Cronstein B.N.
        Adenosine: an endogenous regulator of innate immunity.
        Trends Immunol. 2004; 25: 33-39
        • Johnson R.W.
        The concept of sickness behavior: a brief chronological account of four key discoveries.
        Vet. Immunol. Immunopathol. 2002; 87: 443-450
        • Murray M.J.
        • Murray A.B.
        Anorexia of infection as a mechanism of host defense.
        Am. J. Clin. Nutr. 1979; 32: 593-596
        • Pond C.M.
        Paracrine relationships between adipose and lymphoid tissues: implications for the mechanism of HIV-associated adipose redistribution syndrome.
        Trends Immunol. 2003; 24: 13-18