Exp Clin Endocrinol Diabetes 2016; 124(08): 474-480
DOI: 10.1055/s-0042-106292
Article
© Georg Thieme Verlag KG Stuttgart · New York

Macrophage Infiltration into Subcutaneous Adipose Tissue is Associated with Local Levels of 11BHSD1

H. Korkmaz
1   Endocrinology and Metabolic Disease, Edirne State Hospital, Edirne, Turkey
,
Z. Bozdag
2   Department of Pathology, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
,
E. Akarsu
3   Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
,
M. Tarakcioglu
4   Department of Clinical Biochemistry, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
,
H. Ulusal
4   Department of Clinical Biochemistry, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
,
M. A. Gökalp
5   Department of General Surgery, Faculty of Medicine, Gaziantep University, Sahinbey, Gaziantep, Turkey
› Author Affiliations
Further Information

Publication History

received 25 October 2015
revised 22 February 2016

accepted 11 April 2016

Publication Date:
24 May 2016 (online)

Abstract

The present study aimed to evaluate the infiltration of macrophages in form of crown-line structures (CLS) in subcutaneous adipose tissue (SAT) of obese individuals, and to investigate the effect of these on both metabolic parameters and adipose tissue 11-beta-hydroxysteroid dehydrogenase type 1 (11BHSD1) enzyme levels. A total of 53 obese (10 men, 43 woman) enrolled in the study. Body mass index (BMI), waist circumference (WC), hip circumfrence, and systolic (SBP) and diastolic blood pressures (DBP) of all subjects were recorded. Insulin resistance was determined using the homeostasis model assessment (HOMA). The concentration of SAT, tumor necrosis factor (TNF)-α, interleukin (IL)-6, 11BHSD1 were performed by enzyme-linked immunosorbent assay (ELISA) method. The infiltration of macrophages in form of CLS in adipose tissue were determined using cell-specific stains against CD68. There was no significant difference between the CLS+group and the CLS group in terms of age, gender, BMI, WC, waist-to-hip circumference ratio (WHR), SBP and DBP levels. Fasting plasma glucose (FPG), HOMA-IR, insulin and SAT TNF-α levels were higher in the CLS+group compared to the CLS group. FPG and SAT TNF-α levels were significantly higher in participants with high CLS density compared to participants with low density CLS. SAT 11BHSD1 levels was significant higher in the CLS+group compare to the CLS group and in the high CLS density group compared to the low density group. In conclusion, the infiltration of macrophages in the form of CLS in SAT is associated with increased 11BHSD1 levels. It may be an important mechanism in the development of metabolic disorders.

 
  • References

  • 1 Sowers JR. Update on the cardiometabolic syndrome. Clin Cornerstone 2001; 4: 17-23
  • 2 Despres JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation 2012; 126: 1301-1313
  • 3 Fuentes E, Fuentes F, Vilahur G et al. Mechanisms of chronic state of inflammation as mediators that link obese adipose tissue and metabolic syndrome. Mediators Inflamm 2013; DOI: 10.1155/2013/136584.
  • 4 Bays HE, Gonzalez-Campoy JM, Bray GA et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther 2008; 6: 343-368
  • 5 Mathis D. Immunological goings-on in visceral adipose tissue. Cell Metab 2013; 17: 851-859
  • 6 Esser N, Legrand-Poels S, Piette J et al. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 2014; 105: 141-150
  • 7 Kraakman MJ, Murphy AJ, Jandeleit-Dahm K et al. Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function?. Front Immunol 2014; 5: 470
  • 8 Cinti S, Mitchell G, Barbatelli G et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347-2355
  • 9 Shaul ME, Bennett G, Strissel KJ et al. Dynamic, M2- like remodeling phenotypes of CD11c+adipose tissue macrophages during high-fat diet-induced obesity in mice. Diabetes 2010; 59: 1171-1181
  • 10 Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta 2014; 1842: 446-462
  • 11 Anagnostis P, Katsiki N, Adamidou F et al. 11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the treatment of metabolic syndrome and obesity-related disorders?. Metabolism 2013; 62: 21-33
  • 12 Chapman KE, Coutinho AE, Gray M et al. The role and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in the inflammatory response. Mol Cell Endocrinol 2009; 301: 123-131
  • 13 Makkonen J, Westerbacka J, Kolak M et al. Increased expression of the macrophage markers and of 11beta-HSD-1 in subcutaneous adipose tissue, but not in cultured monocyte-derived macrophages, is associated with liver fat in human obesity. Int J Obes (Lond) 2007; 31: 1617-1625
  • 14 Lindholm J. Cushing’s disease, pseudo-Cushing states and the dexamethasone test: a historical and critical review. Pituitary 2013; 17: 374-380
  • 15 Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998; 21: 2191-2192
  • 16 Bigornia SJ, Farb MG, Mott MM et al. Relation of depot-specific adipose inflammation to insulin resistance in human obesity. Nutr Diabetes 2012; 2: e30
  • 17 Stefan N, Kantartzis K, Machann J et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med 2008; 168: 1609-1616
  • 18 Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013; DOI: 10.1155/2013/139239.
  • 19 Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259: 87-91
  • 20 Kern PA, Ranganathan S, Li C et al. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001; 280: e745-e751
  • 21 Chawla A, Nguyen KD, Goh YP. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 2011; 11: 738-749
  • 22 Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117: 175-184
  • 23 Wentworth JM, Naselli G, Brown WA et al. Pro-inflammatory CD11c+CD206+adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 2010; 59: 1648-1656
  • 24 Murano I, Barbatelli G, Parisani V et al. Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 2008; 9: 1562-1568
  • 25 Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta 2014; 1842: 446-462
  • 26 Wu H, Perrard XD, Wang Q et al. CD11c expression in adipose tissue and blood and its role in diet-induced obesity. Arterioscler Thromb Vasc Biol 2010; 30: 186-192
  • 27 Brake DK, Smith EO, Mersmann H et al. ICAM-1 expression in adipose tissue: effects of diet-induced obesity in mice. Am J Physiol Cell Physiol 2006; 291: 1232-1239
  • 28 Patsouris D, Li PP, Thapar D et al. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 2008; 8: 301-309
  • 29 Dalmas E, Clément K, Guerre-Millo M. Defining macrophage phenotype and function in adipose tissue. Trends Immunol 2011; 32: 307-314
  • 30 Michaud A, Pelletier M, Noël S et al. Markers of macrophage infiltration and measures of lipolysis in human abdominal adipose tissues. Obesity (Silver Spring) 2013; 21: 2342-2349
  • 31 Lee MJ, Pramyothin P, Karastergiou K et al. Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. Biochim Biophys Acta 2014; 1842: 473-481
  • 32 Masuzaki H, Paterson J, Shinyama H et al. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001; 294: 2166-2170
  • 33 Morton NM, Paterson JM, Masuzaki H et al. Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes 2004; 53: 931-938
  • 34 Kotelevtsev Y, Holmes MC, Burchell A et al. 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc Natl Acad Sci USA 1997; 94: 14924-14929
  • 35 Chinetti-Gbaguidi G, Bouhlel MA, Copin C et al. Peroxisome proliferator-activated receptor-γ activation induces 11β-hydroxysteroid dehydrogenase type 1 activity in human alternative macrophages. Arterioscler Thromb Vasc Biol 2012; 32: 677-685