Skip to main content Accessibility help
×
Home

Long-term changes in adipose tissue in human disease

  • Caroline M. Pond (a1)

Abstract

Redistribution of white adipose tissue is a long-term symptom of several chronic diseases. Although the roles of adipocytes in acute illness have been thoroughly studied, how or why short-term responses of adipose tissue to disease sometimes produce long-term redistribution, and the causal relationship between the anatomical changes and the associated metabolic syndromes are poorly understood. The present paper reviews explanations for the redistribution of adipose tissue after infection with HIV, and in Crohn's disease; both conditions that share the peculiarity of selective expansion of certain adipose depots while others are depleted. HIV adipose tissue redistribution syndrome (HARS) develops gradually after several months of infection with the HIV both in untreated patients and in those taking protease inhibitors and nucleoside reverse transcriptase inhibitors. Some current theories about the causes of HARS are critically assessed, and reasons presented for implicating local interactions between the immune system and perinodal adipocytes. Some evolutionary aspects of conspicuous long-term changes in the distribution of human adipose tissue are discussed. Adipose tissue acts as a social signal, indicating dietary history and previous exposure to pathogens. A distinctive symptom of Crohn's disease is selective enlargement of the mesenteric adipose tissue near the diseased lymph nodes and intestine. Perinodal adipocytes have site-specific properties not found in adipocytes from nodeless depots, such as perirenal and epididymal, that may equip them to interact locally with lymph-node lymphoid cells, making polyunsaturated fatty acids selectively and rapidly available to activated immune cells. Studies of the time course of activation of perinodal adipocytes via the lymph nodes they enclose indicate that prolonged or frequent stimulation recruits more adipocytes to control by immune cells, which may lead to selective enlargement of node-containing depots. These concepts suggest hypotheses about HARS and the anomalous development of mesenteric adipose tissue in Crohn's disease that could form the basis for further investigations.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Long-term changes in adipose tissue in human disease
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Long-term changes in adipose tissue in human disease
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Long-term changes in adipose tissue in human disease
      Available formats
      ×

Copyright

Corresponding author

Corresponding Author: Dr Caroline Pond, fax +44 1908 654167, email C.M.Pond@open.ac.uk

References

Hide All
Behrens, GMN, Stoll, M & Schmidt, RE (2000) Lipodystrophy syndrome in HIV infection. What is it, what causes it and how can it be managed? Drug Safety 23, 5776.
Björntorp, P (1996) The regulation of adipose-tissue distribution in humans. International Journal of Obesity 20, 291302.
Björntorp, P (1997) Body fat distribution, insulin resistance, and metabolic diseases. Nutrition 9, 795803.
Brinkman, K, Smeitink, JA, Romijn, JA & Reiss, P (2000) Mitochondrial toxicity of nucleoside analogue reverse transcriptase inhibitors: a looming obstacle for long-term antiretroviral therapy? Current Opinion in Infectious Diseases 13, 11121115.
Calder, PC (1998) Dietary fatty acids and the immune system. Nutrition Reviews 56, S70S83.
Carr, A (2000) HIV protease inhibitor-related lipodystrophy syndrome. Clinical Infectious Diseases 30, S135S142.
Chrousos, GP (2000) The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuroendocrine and target tissue-related causes. International Journal of Obesity 24, S50S55.
Crohn, BB, Ginzburg, L & Oppenheimer, GD (1932) Regional ileitis, a pathologic and clinical entity. Journal of the American Medical Association 99, 13231329.
Dean, GA & Pedersen, NC (1998) Cytokine response in multiple lymphoid tissues during the primary phase of feline immunodeficiency virus infection. Journal of Virology 72, 94369440.
Decsi, T & Koletzko, B (2000) Effects of protein-energy malnutrition and human immunodeficiency virus-1 infection on essential fatty acid metabolism in children. Nutrition 16, 447453.
de la Asuncion, JG, del Olmo, ML, Sastre, J, Millan, A, Pellin, A, Pallardo, FV & Vina, J (1998) AZT treatment induces molecular and ultrastructural oxidative damage to muscle mitochondria: Prevention by antioxidant vitamins. Journal of Clinical Investigation 102, 49.
Desreumaux, P, Ernst, O, Geboes, K, Gambiez, L, Berrebi, D, Müller-Alouf, H, Hafraoui, S, Emilie, D, Ectors, N, Peuchmaur, M, Cortot, A, Capron, M, Auwerx, J & Colombel, JF (1999) Inflammatory alterations in mesenteric adipose tissue in Crohn's disease. Gastroenterology 117, 7381.
Dhurandhar, N, Kulkarni, PR, Ajinkya, SM, Sherikar, AA & Atkinson, RL (1997) Association of adenovirus infection with human obesity. Obesity Research 5, 464469.
Digby, JE (1998) The role of different adipose depots in glutamine metabolism following feeding, fasting and exercise in the guinea-pig. PhD Thesis, The Open University.
Dong, KL, Bausserman, LL, Flynn, MM, Dickinson, BP, Flanigan, TP, Mileno, MD, Tashima, KT & Carpenter, CCJ (1999) Changes in body habitus and serum lipid abnormalities in HIV-positive women on highly active antiretroviral therapy (HAART). Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 21, 107113.
Ellis, RW (1997) Infection and coronary heart disease. Journal of Medical Microbiology 46, 535539.
Engelson, ES, Kotler, DP, Tan, YX, Agin, D, Wang, J, Pierson, RN & Heymsfield, SB (1999) Fat distribution in HIV-infected patients reporting truncal enlargement quantified by whole-body magnetic resonance imaging. American Journal of Clinical Nutrition 69, 11621169.
Farooqi, IS, Yeo, GSH, Keogh, JM, Aminian, S, Jebb, SA, Butler, G, Cheetham, T & O'Rahilly, S (2000) Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. Journal of Clinical Investigation 106, 271279.
Farooqi, S, Rau, H, Whitehead, J & O'Rahilly, S (1998) ob gene mutations and human obesity. Proceedings of the Nutrition Society 57, 471475.
Folstad, I & Karter, AJ (1992) Parasites, bright males, and the immunocompetence handicap. American Naturalist 139, 603622.
Frayn, KN (2000) Visceral fat and insulin resistance – causative or correlative? British Journal of Nutrition 83, S71S77.
Frayn, KN, Khan, K, Coppack, SW & Elia, M (1991) Amino acid metabolism in human subcutaneous adipose tissue in vivo. Clinical Science 80, 471474.
Geerling, BJ, Van Houwelingen, AC, Badart-Smook, A, Stockbrugger, RW & Brummer, JM (1999) Fat intake and fatty acid profile in plasma phospholipids and adipose tissue in patients with Crohn's disease, compared with controls. American Journal of Gastroenterology 94, 410417.
Gerschenson, M, Erhart, SW, Paik, CY, St Claire, MC, Nagashima, K, Skopets, B, Harbaugh, SW, Harbaugh, JW, Quan, W & Poirier, MC (2000) Fetal mitochondrial heart and skeletal muscle damage in Erythrocebus patas monkeys exposed in utero to 3>-azido-3>-deoxythymidine. AIDS Research and Human Retroviruses 16, 635644.
Gervasoni, C, Ridolfo, AL, Trifirò, G, Santambrogio, S, Norbiato, G, Musicco, M, Clerici, M, Galli, M & Moroni, M (1999) Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy. AIDS 13, 465471.
Gimble, JM, Robinson, CE, Wu, X & Kelly, KA (1996) The function of adipocytes in the bone marrow stroma: an update. Bone 19, 421428.
Grünfeld, C & Feingold, KR (1992) Tumor necrosis factor, interleukin, and interferon induced changes in lipid metabolism as part of host defense. Proceedings of the Society for Experimental Biology and Medicine 200, 224227.
Hatano, H, Miller, KD, Yoder, CP, Yanovski, JA, Sebring, NG, Jones, EC & Davey, RT (2000) Metabolic and anthropometric consequences of interruption of highly active antiretroviral therapy. AIDS 14, 19351942.
Horrobin, D (1992) The relationship between schizophrenia, essential fatty acids and eicosanoid metabolism. Prostaglandins, Leukotrienes and Essential Fatty Acids 47, 7177.
Jaquet, D, Lévine, M, Ortega-Rodriguez, E, Faye, A, Polak, M, Vilmer, E & Lévy-Marchal, C (2000) Clinical and metabolic presentation of the lipodystrophic syndrome in HIV-infected children. AIDS 14, 21232128.
Kaur, A, Rosenzweig, M & Johnson, RP (2000) Immunological memory and acquired immunodeficiency syndrome pathogenesis. Philosophical Transactions of the Royal Society of London 355B, 381390.
Kolson, DL, Lavi, E & González-Scarano, F (1998) The effects of human immunodeficiency virus in the central nervous system. Advances in Virus Research 50, 147.
Kotler, DP, Rosenbaum, K, Wang, J & Pierson, RN (1999) Studies of body composition and fat distribution in HIV-infected and control subjects. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 20, 228237.
Laugharne, JDE, Mellor, JE & Peet, M (1996) Fatty acids and schizophrenia. Lipids 31, S163S175.
Lautenbach, E & Lichtenstein, GR (1997) Human immunodeficiency virus infection and Crohn's disease: The role of the CD4 cell in inflammatory bowel disease. Journal of Clinical Gastroenterology 25, 456459.
Lonn, L, Kvist, H, Ernest, I & Sjöström, L (1994) Changes in body-composition and adipose tissue distribution after treatment of women with Cushing's syndrome. Metabolism 43, 15171522.
McGowan, IM, Fairhurst, RM, Shanahan, F & Anton, PA (1997) Mucosal substance P receptor expression in HIV infection and inflammatory bowel disease. Neuroimmunomodulation 4, 7076.
MacQueen, HA, Sadler, D & Mattacks, CA (2000) Dietary fatty acids influence the appearance of tumour necrosis factor-a receptors on adipocytes following an immune challenge. British Journal of Nutrition 84, 387392.
Madge, S, Kinloch-de-Loes, S, Mercey, D, Johnson, MA & Weller, IVD (1999) Lipodystrophy in patients naive to HIV protease inhibitors. AIDS 13, 735737.
Mattacks, CA & Pond, CM (1997) 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. British Journal of Nutrition 77, 621643.
Mattacks, CA & Pond, CM (1999) Interactions of noradrenalin and tumour necrosis factor-a, interleukin-4 and interleukin-6 in the control of lipolysis from adipocytes around lymph nodes. Cytokine 11, 334346.
Mauss, S (2000) HIV-associated lipodystrophy syndrome. AIDS 14, Suppl. 3, S197S207.
Miller, T (2000) Nutrition in paediatric human immunodeficiency virus infection. Proceedings of the Nutrition Society 59, 155162.
Mishina, D, Katsel, P, Brown, ST, Gilberts, ECAM & Greenstein, RJ (1996) On the etiology of Crohn disease. Proceedings of the National Academy of Sciences USA 93, 98169820.
Mohamed-Ali, V, Pinkney, JH & Coppack, SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity 22, 11451158.
Monteleone, G, Biancone, L, Wedel, S & Pallone, F (2000) IL-4 hyporesponsiveness of Crohn's disease mucosal T lymphocytes: a response of polarised Th1 cells. Digestive and Liver Disease 32, 495497.
Moyle, G (2000) Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clinical Therapeutics 22, 911936.
Panse, I, Vasseur, E, Raffin-Sanson, ML, Staroz, F, Rouveix, E & Saiag, P (2000) Lipodystrophy associated with protease inhibitors. British Journal of Dermatology 142, 496500.
Paton, N, Macallan, DC, Griffin, GE & Pazianas, M (1997) Bone mineral density in patients with human immunodeficiency virus infection. Calcified Tissue International 61, 3032.
Peña, AS (1998) Genetics of inflammatory bowel disease – the candidate gene approach: susceptibility versus disease heterogeneity. Digestive Diseases 16, 356363.
Pond, CM (1998) The Fats of Life. Cambridge: Cambridge University Press.
Pond, CM (1999) Physiological specialisation of adipose tissue. Progress in Lipid Research 38, 225248.
Pond, CM & Mattacks, CA (1995) Interactions between adipose tissue around lymph nodes and lymphoid cells in vitro. Journal of Lipid Research 36, 22192231.
Pond, CM & Mattacks, CA (1998) In vivo evidence for the involvement of the adipose tissue surrounding lymph nodes in immune responses. Immunology Letters 63, 159167.
Portillo, MP, Tueros, AI, Perona, JS, Ruiz-Gutiérrez, V, Torres, I & Macarulla, MT (1999) Modifications induced by dietary lipid source in adipose tissue phospholipid fatty acids and their consequences for lipid mobilization. British Journal of Nutrition 82, 319327.
Safrin, S & Grünfeld, C (1999) Fat distribution and metabolic changes in patients with HIV infection. AIDS 13, 24932505.
Saint-Marc, T, Partisani, M, Poizot-Martin, I, Bruno, F, Rouvière, O, Lang, J-M, Gastaut, J-A & Touraine, J-L (1999) A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS 13, 16591667.
Saint-Marc, T, Partisani, M, Poizot-Martin, I, Rouvière, O, Bruno, F, Avellaneda, R, Lang, J-M, Gastaut, J-A & Touraine, J-L (2000) Fat distribution evaluated by computed tomography and metabolic abnormalities in patients undergoing antiretroviral therapy: preliminary results of the LIPOCO study. AIDS 14, 3749.
Shaw, AJ, McLean, KA & Evans, BA (1998) Disorders of fat distribution in HIV infection. International Journal of STD and AIDS 9, 595599.
Sheehan, AL, Warren, BF, Gear, MWL & Shepherd, NA (1992) Fat-wrapping in Crohn's disease: pathological basis and relevance to surgical practice. British Journal of Surgery 79, 955958.
Singh, D (1993) Adaptive significance of female physical attractiveness: the role of waist-to-hip ratio. Journal of Personality and Social Psychology 654, 293307.
Singh, D (1995a) Female health, attractiveness, and desirability for relationships: Role of breast asymmetry and waist-to-hip ratio. Ethology and Sociobiology 16, 465481.
Singh, D (1995b) Female judgment of male attractiveness and desirability for relationships: role of waist-to-hip ratio and financial status. Journal of Personality and Social Psychology 69, 10891101.
Singh, D & Bronstad, PM (1997) Sex differences in the anatomical locations of human body scarification and tattooing as a function of pathogen prevalence. Evolution and Human Behavior 18, 403416.
Singh, D & Luis, S (1995) Ethnic and gender consensus for the effect of waist-to-hip ratio on judgment of women's attractiveness. Human Nature 6, 5165.
Singh, D & Young, RK (1995) Body weight, waist-to-hip ratio, breasts, and hips: role in judgments of female attractiveness and desirability for relationships. Ethology and Sociobiology 16, 483507.
Tebas, P, Powderly, WG, Claxton, S, Marin, D, Tantisiriwat, W, Teitelbaum, SL & Yarasheski, KE (2000) Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS 14, F63F67.
Torpy, DJ, Bornstein, SR & Chrousos, GP (1998) Leptin and interleukin-6 in sepsis. Hormone and Metabolic Research 30, 726729.
Vigouroux, C, Gharakhanian, S, Salhi, Y, Nguyen, TH, Chevenne, D, Capeau, J & Rozenbaum, W (1999) Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART). Diabetes and Metabolism 25, 225232.
Yolken, RH, Karlsson, H, Yee, F, Johnston-Wilson, NL & Torrey, EF (2000) Endogenous retroviruses and schizophrenia. Brain Research Reviews 31, 193199.
Zuk, M (1996) Disease, endocrine-immune interactions, and sexual selection. Ecology 77, 10371042.

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed