Depot- and gender-specific expression of NLRP3 inflammasome and toll-like receptors in adipose tissue of cancer patients.

Gender difference in obesity-associated cardiovascular complication could be derived from divergent chronic inflammation. We evaluated depot- and gender-specific regulation of the innate immune system in human adipose tissues. Pair samples were obtained from subcutaneous (SAT) and visceral adipose tissue (VAT) during elective surgery (Male: 35; Female: 27). Expressions of pro- and anti-inflammatory adipocytokines were evaluated by semi-quantitative qPCR. Adipose cell-size distribution was obtained from tissue samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. Levels of adiponectin were higher in SAT and VAT of female than those of male (P < 0.001 and P = 0.011, respectively). NLRP3, IL1β-IL18, TLR2 were comparable in SAT and VAT between genders. However, TLR4 and TLR9 were increased in female SAT and VAT and HMGB1 in female VAT. Levels of adiponectin were not correlated with mean diameter of adipocyte (φ, μm) in SAT and VAT of male, but negatively well correlated in those of female (r = -0.392 and r = -0.616). Such negative correlations were also observed between levels of TLR2, TLR4, and HMGB1 and φ in female. Levels of NLRP3 and IL1β were positively correlated with φ in male, but not in female. In conclusion, Innate signals were differentially expressed in male and female adipose tissues, suggesting that the depot- and gender-specific signals could be related to gender difference in chronic inflammation. © 2016 BioFactors, 42(4):397-406, 2016.

[1]  I. Imoto,et al.  Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance , 2016, Science Advances.

[2]  J. Ting,et al.  Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components , 2015, Oncotarget.

[3]  Y. Higashikuni,et al.  HMGB1 plays a critical role in vascular inflammation and lesion formation via toll-like receptor 9. , 2013, Atherosclerosis.

[4]  K. Eckardt,et al.  Inflammation and metabolic dysfunction: links to cardiovascular diseases. , 2012, American journal of physiology. Heart and circulatory physiology.

[5]  S. Oertelt-Prigione The influence of sex and gender on the immune response. , 2012, Autoimmunity reviews.

[6]  S. Akira,et al.  The Radioprotective 105/MD-1 Complex Contributes to Diet-Induced Obesity and Adipose Tissue Inflammation , 2012, Diabetes.

[7]  Haitao Wen,et al.  A role for the NLRP3 inflammasome in metabolic diseases—did Warburg miss inflammation? , 2012, Nature Immunology.

[8]  M. Lazar,et al.  Forming functional fat: a growing understanding of adipocyte differentiation , 2011, Nature Reviews Molecular Cell Biology.

[9]  L. Joosten,et al.  Inflammasome is a central player in the induction of obesity and insulin resistance , 2011, Proceedings of the National Academy of Sciences.

[10]  A. C. Könner,et al.  Toll-like receptors: linking inflammation to metabolism , 2011, Trends in Endocrinology & Metabolism.

[11]  Z. Kováčová,et al.  Worsening of obesity and metabolic status yields similar molecular adaptations in human subcutaneous and visceral adipose tissue: decreased metabolism and increased immune response. , 2010, Journal of Clinical Endocrinology and Metabolism.

[12]  E. Ravussin,et al.  The NALP3/NLRP3 Inflammasome Instigates Obesity-Induced Autoinflammation and Insulin Resistance , 2010, Nature Medicine.

[13]  Kohjiro Ueki,et al.  Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus , 2010, Journal of diabetes investigation.

[14]  J. Eckel,et al.  Adipose tissue inflammation: novel insight into the role of macrophages and lymphocytes , 2010, Current opinion in clinical nutrition and metabolic care.

[15]  D. Clegg,et al.  A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice , 2010, International Journal of Obesity.

[16]  S. Akira,et al.  The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors , 2010, Nature Immunology.

[17]  P. Froguel,et al.  Inflammatory Role of Toll-Like Receptors in Human and Murine Adipose Tissue , 2010, Mediators of inflammation.

[18]  A. Veilleux,et al.  Effects of androgens on adipocyte differentiation and adipose tissue explant metabolism in men and women , 2010, Clinical endocrinology.

[19]  泰江 慎太郎 Adipose tissue-specific regulation of angiotensinogen in obese humans and mice : impact of nutritional status and adipocyte hypertrophy , 2010 .

[20]  M. Jensen,et al.  Body fat distribution, adipocyte size, and metabolic characteristics of nondiabetic adults. , 2010, The Journal of clinical endocrinology and metabolism.

[21]  X. Wang,et al.  Macrophage infiltrates with high levels of Toll-like receptor 4 expression in white adipose tissues of male Chinese. , 2009, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[22]  C. Buechler,et al.  Innate Immunity and Adipocyte Function: Ligand‐specific Activation of Multiple Toll‐like Receptors Modulates Cytokine, Adipokine, and Chemokine Secretion in Adipocytes , 2009, Obesity.

[23]  Eric E Schadt,et al.  Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. , 2009, Endocrinology.

[24]  M. Jensen,et al.  Subcutaneous adipocyte size and body fat distribution. , 2008, The American journal of clinical nutrition.

[25]  M. Jensen,et al.  Sex differences in abdominal, gluteal, and thigh LPL activity. , 2007, American journal of physiology. Endocrinology and metabolism.

[26]  C. Herder,et al.  Relationship between adipocyte size and adipokine expression and secretion. , 2007, The Journal of clinical endocrinology and metabolism.

[27]  Y. Matsuki,et al.  Skp2 Controls Adipocyte Proliferation during the Development of Obesity* , 2007, Journal of Biological Chemistry.

[28]  F. Renström,et al.  Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’ , 2007, Diabetologia.

[29]  T. Funahashi,et al.  Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. , 2006, Circulation journal : official journal of the Japanese Circulation Society.

[30]  A. Rissanen,et al.  Acquired obesity increases CD68 and tumor necrosis factor-alpha and decreases adiponectin gene expression in adipose tissue: a study in monozygotic twins. , 2006, The Journal of clinical endocrinology and metabolism.

[31]  Björn Carlsson,et al.  The FASEB Journal • FJ Express Full-Length Article Separation of human adipocytes by size: hypertrophic fat , 2022 .

[32]  W. Wahli,et al.  Nutrigenomics and nutrigenetics: the emerging faces of nutrition , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  M. Kinoshita,et al.  Sex differences in cytokine production and surface antigen expression of peripheral blood mononuclear cells after surgery. , 2005, American journal of surgery.

[34]  J. Katzenellenbogen,et al.  Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha. Implications for the female fat distribution. , 2004, The Journal of clinical endocrinology and metabolism.

[35]  J. Keijer,et al.  Gene expression profiling of adipose tissue: individual, depot-dependent, and sex-dependent variabilities. , 2004, Nutrition.

[36]  M. Matsuda,et al.  Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. , 2002, Diabetes.

[37]  T Nakamura,et al.  Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. , 1999, Biochemical and biophysical research communications.

[38]  Y. Matsuzawa,et al.  Pathophysiology and pathogenesis of visceral fat obesity. , 1995, Annals of the New York Academy of Sciences.

[39]  J. Kral,et al.  Sex differences in regional distribution of fat cell size and lipoprotein lipase activity in morbidly obese patients. , 1987, International journal of obesity.

[40]  L. Sjöström,et al.  Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. , 1983, The Journal of clinical investigation.

[41]  J. Hirsch,et al.  The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. , 1968, The Journal of clinical investigation.