title: B Lymphocyte Stimulator (BLyS) is expressed in human adipocytes in vivo and is related to obesity but not to insulin resistance.
abstract: Inflammation and metabolism have been shown to be evolutionary linked and increasing evidence exists that pro-inflammatory factors are involved in the pathogenesis of obesity and type 2 diabetes. Until now, most data suggest that within adipose tissue these factors are secreted by cells of the innate immune system, e. g. macrophages. In the present study we demonstrate that B lymphocyte stimulator (BLyS) is increased in human obesity. In contrast to several pro-inflammatory factors, we found the source of BLyS in human adipose tissue to be the adipocytes rather than immune cells. In grade 3 obese human subjects, expression of BLyS in vivo in adipose tissue is significantly increased (p<0.001). Furthermore, BLyS serum levels are elevated in grade 3 human obesity (862.5+222.0 pg/ml vs. 543.7+60.7 pg/ml in lean controls, p<0.001) and are positively correlated to the BMI (r = 0.43, p<0.0002). In the present study, bariatric surgery significantly altered serum BLyS concentrations. In contrast, weight loss due to a very-low-calorie-formula-diet (800 kcal/d) had no such effect. To examine metabolic activity of BLyS, in a translational research approach, insulin sensitivity was measured in human subjects in vivo before and after treatment with the human recombinant anti-BLyS antibody belimumab. Since BLyS is known to promote B-cell proliferation and immunoglobulin secretion, the present data suggest that adipocytes of grade 3 obese human subjects are able to activate the adaptive immune system, suggesting that in metabolic inflammation in humans both, innate and adaptive immunity, are of pathophysiological relevance.
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Nike
authors.initials: N
authors.lastname: Müller
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Dominik M
authors.initials: DM
authors.lastname: Schulte
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Hillebrand
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Türk
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.affiliation: Department of General, Abdominal, Thoracic and Transplantation Surgery, University of Kiel, Kiel, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Schafmayer
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Brosch
authors.affiliation: Department of General, Abdominal, Thoracic and Transplantation Surgery, University of Kiel, Kiel, Germany.
authors.forename: Witigo
authors.initials: W
authors.lastname: von Schönfels
authors.affiliation: Department of General, Abdominal, Thoracic and Transplantation Surgery, University of Kiel, Kiel, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Ahrens
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Rainald
authors.initials: R
authors.lastname: Zeuner
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Johann O
authors.initials: JO
authors.lastname: Schröder
authors.affiliation: Department for Internal Medicine, Clinic for Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gutschow
authors.affiliation: Institute of Medical Informatics and Statistics, University of Kiel, Kiel, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Stelmach-Mardas
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Saggau
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Department I of Internal Medicine, University of Kiel, Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Laudes
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000886:Anthropometry; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D053264:B-Cell Activating Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D050110:Bariatric Surgery; D031204:Caloric Restriction; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013851:Thinness / Q000097:blood / Q000150:complications / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D007328:Insulin; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; C511911:belimumab
references.citation: J Biol Chem. 2010 Feb 26;285(9):6170-8
references.pmid: 20032469
references.citation: Nature. 2006 Dec 14;444(7121):875-80
references.pmid: 17167476
references.citation: Mol Med. 2008 Mar-Apr;14(3-4):222-31
references.pmid: 18235842
references.citation: Endocr Rev. 2006 Aug;27(5):449-67
references.pmid: 16684901
references.citation: Trends Immunol. 2007 Sep;28(9):393-9
references.pmid: 17681884
references.citation: Eur J Cardiovasc Prev Rehabil. 2004 Feb;11(1):3-8
references.pmid: 15167200
references.citation: Exp Mol Med. 2009 Mar 31;41(3):208-16
references.pmid: 19293640
references.citation: Ann Intern Med. 2003 Mar 4;138(5):420-3
references.pmid: 12614095
references.citation: Nat Immunol. 2002 Sep;3(9):822-9
references.pmid: 12154359
references.citation: PLoS One. 2012;7(2):e32437
references.pmid: 22384249
references.citation: Obes Surg. 2013 Aug;23(8):1252-61
references.pmid: 23475776
references.citation: J Exp Med. 1999 Jun 7;189(11):1747-56
references.pmid: 10359578
references.citation: Rev Diabet Stud. 2007 Summer;4(2):77-84
references.pmid: 17823691
references.citation: Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1042-7
references.pmid: 12714437
references.citation: Int J Obes (Lond). 2011 Nov;35(11):1450-4
references.pmid: 21285942
references.citation: Science. 1999 Jul 9;285(5425):260-3
references.pmid: 10398604
references.citation: N Engl J Med. 2006 Aug 24;355(8):763-78
references.pmid: 16926275
references.citation: Diabetologia. 2009 Nov;52(11):2345-2349
references.pmid: 19756488
references.citation: Obesity (Silver Spring). 2011 Oct;19(10):1915-22
references.pmid: 21701571
references.citation: Curr Opin Immunol. 2007 Jun;19(3):327-36
references.pmid: 17433868
references.citation: Gastroenterology. 2013 Aug;145(2):366-74.e1-3
references.pmid: 23597726
references.citation: JAMA. 2004 Sep 8;292(10):1188-94
references.pmid: 15353531
references.citation: Blood. 2001 Jan 1;97(1):198-204
references.pmid: 11133761
references.citation: BMC Cancer. 2008 Mar 20;8:76
references.pmid: 18366696
references.citation: Biochim Biophys Acta. 2010 Mar;1801(3):338-49
references.pmid: 20056169
references.citation: PLoS One. 2010 Dec 13;5(12):e14328
references.pmid: 21179199