Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-19T17:39:18.264Z Has data issue: false hasContentIssue false
  • English
  • Français

Long-term changes in adipose tissue in human disease

Published online by Cambridge University Press:  05 March 2007

Caroline M. Pond
Caroline M. Pond*
Affiliation:
Department of Biological Sciences, The Open University, Milton Keynes MK7 6AA, UK
*
Corresponding Author: Dr Caroline Pond, fax +44 1908 654167, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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.

Keywords

HIVHIV adipose redistribution syndromeCrohn’s diseasePerinodal adipocytesAntiretroviral drugs
Type
Symposium on ‘New perspectives on adipose tissue function’
Information
Proceedings of the Nutrition Society , Volume 60 , Issue 3 , August 2001 , pp. 365 - 374
Copyright
Copyright © The Nutrition Society 2001

References

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, 57–76.CrossRefGoogle ScholarPubMed
Björntorp, P (1996) The regulation of adipose-tissue distribution in humans. International Journal of Obesity 20, 291–302.Google ScholarPubMed
Björntorp, P (1997) Body fat distribution, insulin resistance, and metabolic diseases. Nutrition 9, 795–803.CrossRefGoogle Scholar
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, 1112–1115.CrossRefGoogle ScholarPubMed
Calder, PC (1998) Dietary fatty acids and the immune system. Nutrition Reviews 56, S70–S83.CrossRefGoogle ScholarPubMed
Carr, A (2000) HIV protease inhibitor-related lipodystrophy syndrome. Clinical Infectious Diseases 30, S135–S142.CrossRefGoogle ScholarPubMed
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, S50–S55.CrossRefGoogle ScholarPubMed
Crohn, BB, Ginzburg, L & Oppenheimer, GD (1932) Regional ileitis, a pathologic and clinical entity. Journal of the American Medical Association 99, 1323–1329.CrossRefGoogle Scholar
Dean, GA & Pedersen, NC (1998) Cytokine response in multiple lymphoid tissues during the primary phase of feline immunodeficiency virus infection. Journal of Virology 72, 9436–9440.CrossRefGoogle ScholarPubMed
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, 447–453.CrossRefGoogle ScholarPubMed
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, 4–9.CrossRefGoogle ScholarPubMed
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, 73–81.CrossRefGoogle ScholarPubMed
Dhurandhar, N, Kulkarni, PR, Ajinkya, SM, Sherikar, AA & Atkinson, RL (1997) Association of adenovirus infection with human obesity. Obesity Research 5, 464–469.CrossRefGoogle ScholarPubMed
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.Google Scholar
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, 107–113.Google ScholarPubMed
Ellis, RW (1997) Infection and coronary heart disease. Journal of Medical Microbiology 46, 535–539.CrossRefGoogle ScholarPubMed
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, 1162–1169.CrossRefGoogle ScholarPubMed
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, 271–279.CrossRefGoogle ScholarPubMed
Farooqi, S, Rau, H, Whitehead, J & O'Rahilly, S (1998) ob gene mutations and human obesity. Proceedings of the Nutrition Society 57, 471–475.CrossRefGoogle ScholarPubMed
Folstad, I & Karter, AJ (1992) Parasites, bright males, and the immunocompetence handicap. American Naturalist 139, 603–622.CrossRefGoogle Scholar
Frayn, KN (2000) Visceral fat and insulin resistance – causative or correlative? British Journal of Nutrition 83, S71–S77.CrossRefGoogle ScholarPubMed
Frayn, KN, Khan, K, Coppack, SW & Elia, M (1991) Amino acid metabolism in human subcutaneous adipose tissue in vivo. Clinical Science 80, 471–474.CrossRefGoogle ScholarPubMed
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, 410–417.CrossRefGoogle ScholarPubMed
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, 635–644.CrossRefGoogle Scholar
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, 465–471.CrossRefGoogle ScholarPubMed
Gimble, JM, Robinson, CE, Wu, X & Kelly, KA (1996) The function of adipocytes in the bone marrow stroma: an update. Bone 19, 421–428.CrossRefGoogle ScholarPubMed
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, 224–227.CrossRefGoogle ScholarPubMed
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, 1935–1942.CrossRefGoogle ScholarPubMed
Horrobin, D (1992) The relationship between schizophrenia, essential fatty acids and eicosanoid metabolism. Prostaglandins, Leukotrienes and Essential Fatty Acids 47, 71–77.CrossRefGoogle Scholar
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, 2123–2128.CrossRefGoogle ScholarPubMed
Kaur, A, Rosenzweig, M & Johnson, RP (2000) Immunological memory and acquired immunodeficiency syndrome pathogenesis. Philosophical Transactions of the Royal Society of London 355B, 381–390.CrossRefGoogle Scholar
Kolson, DL, Lavi, E & González-Scarano, F (1998) The effects of human immunodeficiency virus in the central nervous system. Advances in Virus Research 50, 1–47.CrossRefGoogle ScholarPubMed
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, 228–237.CrossRefGoogle ScholarPubMed
Laugharne, JDE, Mellor, JE & Peet, M (1996) Fatty acids and schizophrenia. Lipids 31, S163–S175.CrossRefGoogle ScholarPubMed
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, 456–459.CrossRefGoogle ScholarPubMed
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, 1517–1522.CrossRefGoogle ScholarPubMed
McGowan, IM, Fairhurst, RM, Shanahan, F & Anton, PA (1997) Mucosal substance P receptor expression in HIV infection and inflammatory bowel disease. Neuroimmunomodulation 4, 70–76.CrossRefGoogle ScholarPubMed
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, 387–392.CrossRefGoogle Scholar
Madge, S, Kinloch-de-Loes, S, Mercey, D, Johnson, MA & Weller, IVD (1999) Lipodystrophy in patients naive to HIV protease inhibitors. AIDS 13, 735–737.CrossRefGoogle ScholarPubMed
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, 621–643.CrossRefGoogle ScholarPubMed
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, 334–346.CrossRefGoogle Scholar
Mauss, S (2000) HIV-associated lipodystrophy syndrome. AIDS 14, Suppl. 3, S197–S207.Google ScholarPubMed
Miller, T (2000) Nutrition in paediatric human immunodeficiency virus infection. Proceedings of the Nutrition Society 59, 155–162.CrossRefGoogle ScholarPubMed
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, 9816–9820.CrossRefGoogle ScholarPubMed
Mohamed-Ali, V, Pinkney, JH & Coppack, SW (1998) Adipose tissue as an endocrine and paracrine organ. International Journal of Obesity 22, 1145–1158.CrossRefGoogle ScholarPubMed
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, 495–497.CrossRefGoogle ScholarPubMed
Moyle, G (2000) Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clinical Therapeutics 22, 911–936.CrossRefGoogle ScholarPubMed
Panse, I, Vasseur, E, Raffin-Sanson, ML, Staroz, F, Rouveix, E & Saiag, P (2000) Lipodystrophy associated with protease inhibitors. British Journal of Dermatology 142, 496–500.CrossRefGoogle ScholarPubMed
Paton, N, Macallan, DC, Griffin, GE & Pazianas, M (1997) Bone mineral density in patients with human immunodeficiency virus infection. Calcified Tissue International 61, 30–32.CrossRefGoogle ScholarPubMed
Peña, AS (1998) Genetics of inflammatory bowel disease – the candidate gene approach: susceptibility versus disease heterogeneity. Digestive Diseases 16, 356–363.CrossRefGoogle ScholarPubMed
Pond, CM (1998) The Fats of Life. Cambridge: Cambridge University Press.CrossRefGoogle Scholar
Pond, CM (1999) Physiological specialisation of adipose tissue. Progress in Lipid Research 38, 225–248.CrossRefGoogle ScholarPubMed
Pond, CM & Mattacks, CA (1995) Interactions between adipose tissue around lymph nodes and lymphoid cells in vitro. Journal of Lipid Research 36, 2219–2231.CrossRefGoogle ScholarPubMed
Pond, CM & Mattacks, CA (1998) In vivo evidence for the involvement of the adipose tissue surrounding lymph nodes in immune responses. Immunology Letters 63, 159–167.CrossRefGoogle ScholarPubMed
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, 319–327.CrossRefGoogle ScholarPubMed
Safrin, S & Grünfeld, C (1999) Fat distribution and metabolic changes in patients with HIV infection. AIDS 13, 2493–2505.CrossRefGoogle ScholarPubMed
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, 1659–1667.CrossRefGoogle ScholarPubMed
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, 37–49.CrossRefGoogle ScholarPubMed
Shaw, AJ, McLean, KA & Evans, BA (1998) Disorders of fat distribution in HIV infection. International Journal of STD and AIDS 9, 595–599.CrossRefGoogle ScholarPubMed
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, 955–958.CrossRefGoogle ScholarPubMed
Singh, D (1993) Adaptive significance of female physical attractiveness: the role of waist-to-hip ratio. Journal of Personality and Social Psychology 654, 293–307.CrossRefGoogle Scholar
Singh, D (1995a) Female health, attractiveness, and desirability for relationships: Role of breast asymmetry and waist-to-hip ratio. Ethology and Sociobiology 16, 465–481.CrossRefGoogle Scholar
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, 1089–1101.CrossRefGoogle ScholarPubMed
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, 403–416.CrossRefGoogle Scholar
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, 51–65.CrossRefGoogle ScholarPubMed
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, 483–507.CrossRefGoogle Scholar
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, F63–F67.CrossRefGoogle ScholarPubMed
Torpy, DJ, Bornstein, SR & Chrousos, GP (1998) Leptin and interleukin-6 in sepsis. Hormone and Metabolic Research 30, 726–729.CrossRefGoogle ScholarPubMed
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, 225–232.Google ScholarPubMed
Yolken, RH, Karlsson, H, Yee, F, Johnston-Wilson, NL & Torrey, EF (2000) Endogenous retroviruses and schizophrenia. Brain Research Reviews 31, 193–199.CrossRefGoogle ScholarPubMed
Zuk, M (1996) Disease, endocrine-immune interactions, and sexual selection. Ecology 77, 1037–1042.CrossRefGoogle Scholar