期刊论文详细信息
BMC Endocrine Disorders
Adiponectin, chemerin, cytokines, and dipeptidyl peptidase 4 are released from human adipose tissue in a depot-dependent manner: an in vitro system including human serum albumin
Malin Lönn2  Staffan Edén1  Birgitta Odén3  Henrik Svensson3 
[1] Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, S-405 30 Gothenburg, Sweden;Department of Clinical Chemistry, Sahlgrenska University Hospital, Bruna stråket 16, S-413 45 Gothenburg, Sweden;Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, S-405 30 Gothenburg, Sweden
关键词: Human serum albumin;    Bovine serum albumin;    Inflammation;    Insulin resistance;    Metabolic disease;    Visceral adipose tissue;    Subcutaneous adipose tissue;    Cytokines;    Adipokines;   
Others  :  1085328
DOI  :  10.1186/1472-6823-14-7
 received in 2013-07-19, accepted in 2014-01-16,  发布年份 2014
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【 摘 要 】

Background

Adipose tissue (AT) contributes to metabolic dysfunction through imbalanced production of adipokines, including cytokines. Visceral AT in particular is associated with metabolic disorders, indicating a specific secretory status. The relative significance of different human AT depots in adipokine release is not fully known. Further, previous in vitro systems usually included medium containing bovine serum albumin (BSA), which may induce cytokine release. Our aim was to compare release of a number of adipokines/cytokines – all implicated in insulin resistance – from human subcutaneous and visceral AT in a short-term incubation system minimizing cytokine induction and including repeated measurements during 24 h. A prerequisite was to evaluate a potential alternative to BSA in the incubation medium.

Methods

Subcutaneous and/or visceral AT from 17 patients (age 20–68 years; BMI 22.6–56.7 kg/m2) undergoing elective surgery was incubated for 2, 4, 6, 8, and 24 h in medium with or without 1% BSA or human serum albumin (HSA). Medium concentrations of adiponectin, chemerin, nine cytokines, dipeptidyl peptidase 4 (DPP4), and omentin were analyzed by multiplex immunoassay or ELISA. Adipocyte size, AT macrophage density, and medium concentrations of endotoxin were determined.

Results

Cytokine release was induced by BSA but not by HSA. In evaluation of the final incubation protocol including 1% HSA, and as expected, adiponectin release was higher from subcutaneous biopsies of nonobese than of obese subjects and inversely associated with adipocyte size; omentin was released almost exclusively from visceral AT. Exploratory incubations revealed more abundant release of chemerin, cytokines (except IL-6), and DPP4 from the visceral depot, while adiponectin release was higher from subcutaneous than visceral AT. Release was linear for a maximum of 2–6 h. Macrophage density was higher in visceral than subcutaneous AT. Levels of endotoxin in the medium were negligible.

Conclusions

Adiponectin, chemerin, many cytokines, and DPP4 are released from human AT in a depot-dependent manner. These results highlight functional differences between visceral and subcutaneous AT, and a mechanistic link between regional fat accumulation and metabolic disorders. Supplementation of human AT incubation medium with HSA rather than BSA is recommended to minimize induction of cytokine release.

【 授权许可】

   
2014 Svensson et al.; licensee BioMed Central Ltd.

【 预 览 】
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【 参考文献 】
  • [1]Kershaw EE, Flier JS: Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004, 89(6):2548-2556.
  • [2]Ahima RS, Osei SY: Adipokines in obesity. Front Horm Res 2008, 36:182-197.
  • [3]Deng Y, Scherer PE: Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci 2010, 1212:E1-E19.
  • [4]Ouchi N, Parker JL, Lugus JJ, Walsh K: Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011, 11(2):85-97.
  • [5]Hotamisligil GS: Inflammation and metabolic disorders. Nature 2006, 444(7121):860-867.
  • [6]Preis SR, Massaro JM, Robins SJ, Hoffmann U, Vasan RS, Irlbeck T, Meigs JB, Sutherland P, D’Agostino RB Sr, O’Donnell CJ, et al.: Abdominal subcutaneous and visceral adipose tissue and insulin resistance in the Framingham heart study. Obesity (Silver Spring) 2010, 18(11):2191-2198.
  • [7]Sam S, Haffner S, Davidson MH, D’Agostino RB Sr, Feinstein S, Kondos G, Perez A, Mazzone T: Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes. Diabetes 2008, 57(8):2022-2027.
  • [8]Jernas M, Palming J, Sjoholm K, Jennische E, Svensson PA, Gabrielsson BG, Levin M, Sjogren A, Rudemo M, Lystig TC, et al.: Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. FASEB J 2006, 20(9):1540-1542.
  • [9]Anderson EK, Gutierrez DA, Hasty AH: Adipose tissue recruitment of leukocytes. Curr Opin Lipidol 2010, 21(3):172-177.
  • [10]Alvehus M, Buren J, Sjostrom M, Goedecke J, Olsson T: The human visceral fat depot has a unique inflammatory profile. Obesity (Silver Spring) 2010, 18(5):879-883.
  • [11]Gabrielsson BG, Johansson JM, Lonn M, Jernas M, Olbers T, Peltonen M, Larsson I, Lonn L, Sjostrom L, Carlsson B, et al.: High expression of complement components in omental adipose tissue in obese men. Obes Res 2003, 11(6):699-708.
  • [12]Samaras K, Botelho NK, Chisholm DJ, Lord RV: Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring) 2010, 18(5):884-889.
  • [13]Fried SK, Bunkin DA, Greenberg AS: Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998, 83(3):847-850.
  • [14]Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, Arner P: Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998, 47(6):913-917.
  • [15]Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW: Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004, 145(5):2273-2282.
  • [16]Sopasakis VR, Sandqvist M, Gustafson B, Hammarstedt A, Schmelz M, Yang X, Jansson PA, Smith U: High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator. Obes Res 2004, 12(3):454-460.
  • [17]Madani R, Karastergiou K, Ogston NC, Miheisi N, Bhome R, Haloob N, Tan GD, Karpe F, Malone-Lee J, Hashemi M, et al.: RANTES release by human adipose tissue in vivo and evidence for depot-specific differences. Am J Physiol Endocrinol Metab 2009, 296(6):E1262-E1268.
  • [18]Carswell KA, Lee MJ, Fried SK: Culture of isolated human adipocytes and isolated adipose tissue. Methods Mol Biol 2012, 806:203-214.
  • [19]Arner P: Techniques for the measurement of white adipose tissue metabolism: a practical guide. Int J Obes Relat Metab Disord 1995, 19(7):435-442.
  • [20]Schlesinger JB, van Harmelen V, Alberti-Huber CE, Hauner H: Albumin inhibits adipogenesis and stimulates cytokine release from human adipocytes. Am J Physiol Cell Physiol 2006, 291(1):C27-C33.
  • [21]Ottosson M, Vikman-Adolfsson K, Enerback S, Elander A, Bjorntorp P, Eden S: Growth hormone inhibits lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 1995, 80(3):936-941.
  • [22]Ottosson M, Lonnroth P, Bjorntorp P, Eden S: Effects of cortisol and growth hormone on lipolysis in human adipose tissue. J Clin Endocrinol Metab 2000, 85(2):799-803.
  • [23]Smith U, Sjostrom L, Bjornstorp P: Comparison of two methods for determining human adipose cell size. J Lipid Res 1972, 13(6):822-824.
  • [24]Bjornheden T, Jakubowicz B, Levin M, Oden B, Eden S, Sjostrom L, Lonn M: Computerized determination of adipocyte size. Obes Res 2004, 12(1):95-105.
  • [25]Goldrick RB: Morphological changes in the adipocyte during fat deposition and mobilization. Am J Physiol 1967, 212(4):777-782.
  • [26]Kuehl RO: Design of experiments: statistical principles of research design and analysis. 2nd edition. Pacific Grove: Duxbury-Thomson Learning; 2000.
  • [27]Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, et al.: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999, 257(1):79-83.
  • [28]Turer AT, Khera A, Ayers CR, Turer CB, Grundy SM, Vega GL, Scherer PE: Adipose tissue mass and location affect circulating adiponectin levels. Diabetologia 2011, 54(10):2515-2524.
  • [29]Bahceci M, Gokalp D, Bahceci S, Tuzcu A, Atmaca S, Arikan S: The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? J Endocrinol Invest 2007, 30(3):210-214.
  • [30]Hammarstedt A, Graham TE, Kahn BB: Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells. Diabetology & Metabolic Syndrome 2012, 4(1):42. BioMed Central Full Text
  • [31]Murdolo G, Hammarstedt A, Schmelz M, Jansson PA, Smith U: Acute hyperinsulinemia differentially regulates interstitial and circulating adiponectin oligomeric pattern in lean and insulin-resistant, obese individuals. J Clin Endocrinol Metab 2009, 94(11):4508-4516.
  • [32]Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, Gong DW: Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006, 290(6):E1253-E1261.
  • [33]Auguet T, Quintero Y, Riesco D, Morancho B, Terra X, Crescenti A, Broch M, Aguilar C, Olona M, Porras JA, et al.: New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women. BMC Med Gen 2011, 12:60.
  • [34]Wheeler DS, Giuliano JS Jr, Lahni PM, Denenberg A, Wong HR, Zingarelli B: The immunomodulatory effects of albumin in vitro and in vivo. Adv Phar Sc 2011, 2011:691928.
  • [35]Zhong WW, Burke PA, Hand AT, Walsh MJ, Hughes LA, Forse RA: Regulation of cytokine mRNA expression in lipopolysaccharide-stimulated human macrophages. Arch Surg 1993, 128(2):158-163. discussion 163–154
  • [36]Hoch M, Eberle AN, Peterli R, Peters T, Seboek D, Keller U, Muller B, Linscheid P: LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-alpha in human adipocytes. Cytokine 2008, 41(1):29-37.
  • [37]Arbabi S, Garcia I, Bauer GJ, Maier RV: Alcohol (ethanol) inhibits IL-8 and TNF: role of the p38 pathway. J Immunol 1999, 162(12):7441-7445.
  • [38]Turer AT, Scherer PE: Adiponectin: mechanistic insights and clinical implications. Diabetologia 2012, 55(9):2319-2326.
  • [39]Kishida K, Kim KK, Funahashi T, Matsuzawa Y, Kang HC, Shimomura I: Relationships between circulating adiponectin levels and fat distribution in obese subjects. J Atheroscler Thromb 2011, 18(7):592-595.
  • [40]Kovacova Z, Tencerova M, Roussel B, Wedellova Z, Rossmeislova L, Langin D, Polak J, Stich V: The impact of obesity on secretion of adiponectin multimeric isoforms differs in visceral and subcutaneous adipose tissue. Int J Obes (Lond) 2012, 36(10):1360-1365.
  • [41]Phillips SA, Ciaraldi TP, Oh DK, Savu MK, Henry RR: Adiponectin secretion and response to pioglitazone is depot dependent in cultured human adipose tissue. Am J Physiol Endocrinol Metab 2008, 295(4):E842-E850.
  • [42]Motoshima H, Wu X, Sinha MK, Hardy VE, Rosato EL, Barbot DJ, Rosato FE, Goldstein BJ: Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. J Clin Endocrinol Metab 2002, 87(12):5662-5667.
  • [43]Drolet R, Belanger C, Fortier M, Huot C, Mailloux J, Legare D, Tchernof A: Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women. Obesity (Silver Spring) 2009, 17(3):424-430.
  • [44]Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B: Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Mol Cell Endocrinol 2004, 219(1–2):9-15.
  • [45]Hernandez-Morante JJ, Milagro FI, Larque E, Lujan J, Martinez JA, Zamora S, Garaulet M: Relationship among adiponectin, adiponectin gene expression and fatty acids composition in morbidly obese patients. Obes Surg 2007, 17(4):516-524.
  • [46]Sell H, Laurencikiene J, Taube A, Eckardt K, Cramer A, Horrighs A, Arner P, Eckel J: Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes 2009, 58(12):2731-2740.
  • [47]Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, Muruganandan S, Sinal CJ: Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007, 282(38):28175-28188.
  • [48]Rourke JL, Dranse HJ, Sinal CJ: Towards an integrative approach to understanding the role of chemerin in human health and disease. Obes Rev 2012, 2012:2012.
  • [49]Chakaroun R, Raschpichler M, Kloting N, Oberbach A, Flehmig G, Kern M, Schon MR, Shang E, Lohmann T, Dressler M, et al.: Effects of weight loss and exercise on chemerin serum concentrations and adipose tissue expression in human obesity. Metabolism 2012, 61(5):706-714.
  • [50]Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens DM, Eckardt K, Kaufman JM, Ryden M, Muller S, et al.: Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 2011, 60(7):1917-1925.
  • [51]Kos K, Baker AR, Jernas M, Harte AL, Clapham JC, O’Hare JP, Carlsson L, Kumar S, McTernan PG: DPP-IV inhibition enhances the antilipolytic action of NPY in human adipose tissue. Diabetes Obes Metab 2009, 11(4):285-292.
  • [52]Lapice E, Maione S, Patti L, Cipriano P, Rivellese AA, Riccardi G, Vaccaro O: Abdominal adiposity is associated with elevated C-reactive protein independent of BMI in healthy nonobese people. Diabetes Care 2009, 32(9):1734-1736.
  • [53]Cartier A, Lemieux I, Almeras N, Tremblay A, Bergeron J, Despres JP: Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men. J Clin Endocrinol Metab 2008, 93(5):1931-1938.
  • [54]Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S: Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007, 56(4):1010-1013.
  • [55]Bruun JM, Lihn AS, Madan AK, Pedersen SB, Schiott KM, Fain JN, Richelsen B: Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Physiol Endocrinol Metab 2004, 286(1):E8-E13.
  • [56]Koenen TB, Stienstra R, van Tits LJ, Joosten LA, van Velzen JF, Hijmans A, Pol JA, van der Vliet JA, Netea MG, Tack CJ, et al.: The inflammasome and caspase-1 activation: a new mechanism underlying increased inflammatory activity in human visceral adipose tissue. Endocrinology 2011, 152(10):3769-3778.
  • [57]Eriksson P, Van Harmelen V, Hoffstedt J, Lundquist P, Vidal H, Stemme V, Hamsten A, Arner P, Reynisdottir S: Regional variation in plasminogen activator inhibitor-1 expression in adipose tissue from obese individuals. Thromb Haemostasis 2000, 83(4):545-548.
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