Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome

BMC Infectious Diseases

José Luís Medina²  António Sarmento¹  Jorge Pereira⁴  Esteban Martinez⁵  António José Madureira³  Ana Cristina Santos⁶  Davide Carvalho²  Paula Freitas² 

[1] Infectious Diseases Department, Hospital de São João and University of Porto Medical School, Porto, Portugal;Endocrinology Department, Hospital de São João and University of Porto Medical School, Alameda Hernâni Monteiro, 4200 Porto, Portugal;Radiology Department, Hospital de São João and University of Porto Medical School, Porto, Portugal;Nuclear Medicine Department, Hospital de São João, Porto, Portugal;Department of Infectious Diseases, Hospital Clinic, University of Barcelona Medical School, Barcelona, Spain;University of Porto Institute of Public Health, Porto, Portugal

关键词: Insulin resistance;    Body composition;    Adipokines;    HIV;    Lipodystrophy;   

Others  :  1127497
DOI  :  10.1186/1471-2334-14-347

 received in 2013-09-12, accepted in 2014-06-13,  发布年份 2014

【 摘 要 】

Background

Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution.

Methods

Anthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient’s fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation.

Results

Leptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching.

Conclusion

The overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.

【 授权许可】

   
2014 Freitas et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Garg A: Acquired and inherited lipodystrophies. N Engl J Med 2004, 350(12):1220-1234.
• [2]Veloso S, Escote X, Ceperuelo-Mallafre V, Lopez-Dupla M, Peraire J, Vilades C, Domingo P, Castro A, Olona M, Sirvent JJ, Leal M, Vendrell J, Richart C, Vidal F: Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy. Cytokine 2012, 58(2):253-260.
• [3]Ronti T, Lupattelli G, Mannarino E: The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf) 2006, 64(4):355-365.
• [4]Falasca K, Ucciferri C, Mancino P, Di Iorio A, Vignale F, Pizzigallo E, Vecchiet J: Cystatin C, adipokines and cardiovascular risk in HIV infected patients. Curr HIV Res 2010, 8(5):405-410.
• [5]Koutkia P, Meininger G, Canavan B, Breu J, Grinspoon S: Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy. Am J Physiol Endocrinol Metab 2004, 286(2):E296-E303.
• [6]Sweeney LL, Brennan AM, Mantzoros CS: The role of adipokines in relation to HIV lipodystrophy. AIDS 2007, 21(8):895-904.
• [7]Samaras K, Gan SK, Peake PW, Carr A, Campbell LV: Proinflammatory markers, insulin sensitivity, and cardiometabolic risk factors in treated HIV infection. Obesity (Silver Spring) 2009, 17(1):53-59.
• [8]Santos AC, Ebrahim S, Barros H: Gender, socio-economic status and metabolic syndrome in middle-aged and old adults. BMC Public Health 2008, 8:62.
• [9]CDC: Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Recomm Rep 1993, 41:1-19.
• [10]Freitas P, Santos AC, Carvalho D, Pereira J, Marques R, Martinez E, Sarmento A, Medina JL: Fat mass ratio: an objective tool to define lipodystrophy in hiv-infected patients under antiretroviral therapy. J Clin Densitom 2010, 13(2):197-203.
• [11]Freitas P, Carvalho D, Santos AC, Mesquita J, Correia F, Xerinda S, Marques R, Martinez E, Sarmento A, Medina JL: Assessment of body fat composition disturbances by bioimpedance analysis in HIV-infected adults. J Endocrinol Investig 2011, 34(10):e321-e329.
• [12]Freitas P, Carvalho D, Santos AC, Matos MJ, Madureira AJ, Marques R, Martinez E, Sarmento A, Medina JL: Prevalence of obesity and its relationship to clinical lipodystrophy in HIV-infected adults on anti-retroviral therapy. J Endocrinol Investig 2012, 35(11):964-970.
• [13]Freitas P, Carvalho D, Souto S, Santos AC, Xerinda S, Marques R, Martinez E, Sarmento A, Medina JL: Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients. BMC Infect Dis 2011, 11:246.
• [14]Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ, National Heart, Lung Blood Institute Joint National Committee on Prevention, Detection Evaluation Treatment of High Blood, Pressure: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003, 289(19):2560-2572.
• [15]Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr: Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009, 120(16):1640-1645.
• [16]Bonnet E, Delpierre C, Sommet A, Marion-Latard F, Herve R, Aquilina C, Labau E, Obadia M, Marchou B, Massip P, Perret B, Bernard J: Total body composition by DXA of 241 HIV-negative men and 162 HIV-infected men: proposal of reference values for defining lipodystrophy. J Clin Densitom 2005, 8(3):287-292.
• [17]van der Kooy K, Seidell JC: Techniques for the measurement of visceral fat: a practical guide. Int J Obes Relat Metab Disord 1993, 17(4):187-196.
• [18]Yoshizumi T, Nakamura T, Yamane M, Islam AH, Menju M, Yamasaki K, Arai T, Kotani K, Funahashi T, Yamashita S, Matsuzawa Y: Abdominal fat: standardized technique for measurement at CT. Radiology 1999, 211(1):283-286.
• [19]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28(7):412-419.
• [20]Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000, 85(7):2402-2410.
• [21]Grinspoon S: Insulin resistance in the HIV-lipodystrophy syndrome. Trends Endocrinol Metab 2001, 12(9):413-419.
• [22]Reitman ML, Arioglu E, Gavrilova O, Taylor SI: Lipoatrophy revisited. Trends Endocrinol Metab 2000, 11(10):410-416.
• [23]Hegele RA: Insulin resistance in human partial lipodystrophy. Curr Atheroscler Rep 2000, 2(5):397-404.
• [24]Mynarcik DC, Combs T, McNurlan MA, Scherer PE, Komaroff E, Gelato MC: Adiponectin and leptin levels in HIV-infected subjects with insulin resistance and body fat redistribution. J Acquir Immune Defic Syndr 2002, 31(5):514-520.
• [25]Gougeon ML, Penicaud L, Fromenty B, Leclercq P, Viard JP, Capeau J: Adipocytes targets and actors in the pathogenesis of HIV-associated lipodystrophy and metabolic alterations. Antivir Ther 2004, 9(2):161-177.
• [26]Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996, 334(5):292-295.
• [27]Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999, 257(1):79-83.
• [28]Vigouroux C, Maachi M, Nguyen TH, Coussieu C, Gharakhanian S, Funahashi T, Matsuzawa Y, Shimomura I, Rozenbaum W, Capeau J, Bastard JP: Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS 2003, 17(10):1503-1511.
• [29]Haque WA, Shimomura I, Matsuzawa Y, Garg A: Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab 2002, 87(5):2395.
• [30]Kosmiski LA, Bacchetti P, Kotler DP, Heymsfield SB, Lewis CE, Shlipak MG, Scherzer R, Grunfeld C: Relationship of fat distribution with adipokines in human immunodeficiency virus infection. J Clin Endocrinol Metab 2008, 93(1):216-224.
• [31]Martini G, Valenti R, Giovani S, Campagna S, Franci B, Nuti R: Leptin and body composition in healthy postmenopausal women. Panminerva Med 2001, 43(3):149-154.
• [32]Wunder D, Bersinger NA, Fux C, Weber R, Bernasconi E, Cavassini M, Bucher HC, Schiffer V, Schmid P, Furrer H: Plasma leptin levels in men are not related to the development of lipoatrophy during antiretroviral therapy. AIDS 2005, 19(16):1837-1842.
• [33]Koutkia P, Canavan B, Breu J, Johnson ML, Depaoli A, Grinspoon SK: Relation of leptin pulse dynamics to fat distribution in HIV-infected patients. Am J Clin Nutr 2004, 79(6):1103-1109.
• [34]Freitas PCD, Santos AC, Xerinda S, Matos MJ, Marques R, Serrão R, Pereira J, Sarmento A, Medina JL: A one year prospective study indicates that HIV patients under antiretroviral therapy worsen lipodystrophy. Arq Bras Endocrinol Metabol 2008, 52:S945.
• [35]Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A: Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002, 346(8):570-578.
• [36]Tong Q, Sankale JL, Hadigan CM, Tan G, Rosenberg ES, Kanki PJ, Grinspoon SK, Hotamisligil GS: Regulation of adiponectin in human immunodeficiency virus-infected patients: relationship to body composition and metabolic indices. J Clin Endocrinol Metab 2003, 88(4):1559-1564.
• [37]Addy CL, Gavrila A, Tsiodras S, Brodovicz K, Karchmer AW, Mantzoros CS: Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrinol Metab 2003, 88(2):627-636.
• [38]Delporte ML, Brichard SM, Hermans MP, Beguin C, Lambert M: Hyperadiponectinaemia in anorexia nervosa. Clin Endocrinol (Oxf) 2003, 58(1):22-29.
• [39]Wong SP, Huda M, English P, Bargiotta A, Wilding JP, Johnson A, Corrall R, Pinkney JH: Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C. Diabetologia 2005, 48(12):2641-2649.
• [40]Savage DB, Tan GD, Acerini CL, Jebb SA, Agostini M, Gurnell M, Williams RL, Umpleby AM, Thomas EL, Bell JD, Dixon AK, Dunne F, Boiani R, Cinti S, Vidal-Puig A, Karpe F, Chatterjee VK, O'Rahilly S: Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes 2003, 52(4):910-917.
• [41]Kosmiski L, Kuritzkes D, Lichtenstein K, Eckel R: Adipocyte-derived hormone levels in HIV lipodystrophy. Antivir Ther 2003, 8(1):9-15.
• [42]Mynarcik DC, McNurlan MA, Steigbigel RT, Fuhrer J, Gelato MC: Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J Acquir Immune Defic Syndr 2000, 25(4):312-321.
• [43]Estrada V, Martinez-Larrad MT, Gonzalez-Sanchez JL, De Villar NG, Zabena C, Fernandez C, Serrano-Rios M: Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy. Metabolism 2006, 55(7):940-945.
• [44]Chaparro J, Reeds DN, Wen W, Xueping E, Klein S, Semenkovich CF, Bae KT, Quirk EK, Powderly WG, Yarasheski KE, Li E: Alterations in thigh subcutaneous adipose tissue gene expression in protease inhibitor-based highly active antiretroviral therapy. Metabolism 2005, 54(5):561-567.
• [45]Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003, 149(4):331-335.
• [46]Lee JH, Chan JL, Yiannakouris N, Kontogianni M, Estrada E, Seip R, Orlova C, Mantzoros CS: Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 2003, 88(10):4848-4856.
• [47]Youn BS, Yu KY, Park HJ, Lee NS, Min SS, Youn MY, Cho YM, Park YJ, Kim SY, Lee HK, Park KS: Plasma resistin concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 2004, 89(1):150-156.
• [48]Barb D, Wadhwa SG, Kratzsch J, Gavrila A, Chan JL, Williams CJ, Karchmer AW, Mantzoros CS: Circulating resistin levels are not associated with fat redistribution, insulin resistance, or metabolic profile in patients with the highly active antiretroviral therapy-induced metabolic syndrome. J Clin Endocrinol Metab 2005, 90(9):5324-5328.
• [49]Escote X, Miranda M, Veloso S, Domingo P, Alonso-Villaverde C, Peraire J, Vilades C, Alba V, Olona M, Castro A, Lopez-Dupla M, Sirvent JJ, Vicente V, Vendrell J, Richart C, Vidal F, and HIV Lipodystrophy Study Group: Lipodystrophy and insulin resistance in combination antiretroviral treated HIV-1-infected patients: implication of resistin. J Acquir Immune Defic Syndr 2011, 57(1):16-23.
• [50]Kamin D, Hadigan C, Lehrke M, Mazza S, Lazar MA, Grinspoon S: Resistin levels in human immunodeficiency virus-infected patients with lipoatrophy decrease in response to rosiglitazone. J Clin Endocrinol Metab 2005, 90(6):3423-3426.
• [51]Johnson JA, Albu JB, Engelson ES, Fried SK, Inada Y, Ionescu G, Kotler DP: Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy. Am J Physiol Endocrinol Metab 2004, 286(2):E261-E271.
• [52]Hauner H: Secretory factors from human adipose tissue and their functional role. Proc Nutr Soc 2005, 64(2):163-169.
• [53]Vidal F, Domingo P, Vilades C, Peraire J, Arnedo M, Alcami J, Leal M, Villarroya F, Gatell JM: Pharmacogenetics of the lipodystrophy syndrome associated with HIV infection and combination antiretroviral therapy. Expert Opin Drug Metab Toxicol 2011, 7(11):1365-1382.
• [54]Domingo P, Vidal F, Domingo JC, Veloso S, Sambeat MA, Torres F, Sirvent JJ, Vendrell J, Matias-Guiu X, Richart C, HIV-Frs Study Group: Tumour necrosis factor alpha in fat redistribution syndromes associated with combination antiretroviral therapy in HIV-1-infected patients: potential role in subcutaneous adipocyte apoptosis. Eur J Clin Investig 2005, 35(12):771-780.
• [55]Yki-Jarvinen H, Sutinen J, Silveira A, Korsheninnikova E, Fisher RM, Kannisto K, Ehrenborg E, Eriksson P, Hamsten A: Regulation of plasma PAI-1 concentrations in HAART-associated lipodystrophy during rosiglitazone therapy. Arterioscler Thromb Vasc Biol 2003, 23(4):688-694.
• [56]Hadigan C, Meigs JB, Rabe J, D’Agostino RB, Wilson PW, Lipinska I, Tofler GH, Grinspoon SS: Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance. J Clin Endocrinol Metab 2001, 86(2):939-943.
• [57]He G, Andersen O, Haugaard SB, Lihn AS, Pedersen SB, Madsbad S, Richelsen B: Plasminogen activator inhibitor type 1 (PAI-1) in plasma and adipose tissue in HIV-associated lipodystrophy syndrome. Implications of adipokines. Eur J Clin Invest 2005, 35(9):583-590.
• [58]Falasca K, Manigrasso MR, Racciatti D, Zingariello P, Dalessandro M, Ucciferri C, Mancino P, Marinopiccoli M, Petrarca C, Conti P, Pizzigallo E, Guagnano MT, Vecchiet J: Associations between hypertriglyceridemia and serum ghrelin, adiponectin, and IL-18 levels in HIV-infected patients. Ann Clin Lab Sci 2006, 36(1):59-66.
• [59]Rietschel P, Hadigan C, Corcoran C, Stanley T, Neubauer G, Gertner J, Grinspoon S: Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy. J Clin Endocrinol Metab 2001, 86(2):504-510.