title: Adipokine expression and secretion by canine adipocytes: stimulation of inflammatory adipokine production by LPS and TNFalpha.
abstract: Adiposity and obesity are increasing in dogs. We have examined here the endocrine function of canine adipose tissue and the regulation of production of inflammation-related adipokines by dog adipocytes. Adiponectin, leptin, IL-6, MCP-1 and TNFalpha genes were expressed in the main adipose depots of dogs, but there were no major depot differences in mRNA levels. Each adipokine was expressed in canine adipocytes differentiated in culture and secreted into the medium (leptin undetected). IL-6, MCP-1 and TNFalpha were also expressed and secreted by preadipocytes; adiponectin and leptin were only expressed after adipocyte differentiation. The inflammatory mediators LPS and TNFalpha had major stimulatory effects on the expression and secretion of IL-6, MCP-1 and TNFalpha; there was a >5,000-fold increase in IL-6 mRNA level with LPS. IL-6 release into the medium was increased >50-fold over 24 h with LPS and TNFalpha, while MCP-1 release was increased 23- and 40-fold by TNFalpha and LPS, respectively. However, there was no effect, or small reductions, in adiponectin and leptin mRNA levels with the inflammatory mediators. Dexamethasone-stimulated leptin gene expression, had no effect on adiponectin expression, but decreased the expression and secretion of IL-6 and MCP-1. The PPARgamma agonist rosiglitazone stimulated both adiponectin and leptin expression and inhibited the expression of IL-6, MCP-1 and TNFalpha; MCP-1 secretion was reduced. These results demonstrate that canine adipocytes express and secrete key adipokines and show that adipocytes of this species are highly responsive to inflammatory mediators with the induction of major increases in the production of inflammation-related adipokines.
authors.affiliation: Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Duncan Building, Liverpool, L69 3GA, UK.
authors.forename: Vivien H
authors.initials: VH
authors.lastname: Ryan
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: German
authors.forename: I Stuart
authors.initials: IS
authors.lastname: Wood
authors.forename: Leif
authors.initials: L
authors.lastname: Hunter
authors.forename: Penelope
authors.initials: P
authors.lastname: Morris
authors.forename: Paul
authors.initials: P
authors.lastname: Trayhurn
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003907:Dexamethasone; D004285:Dogs; D005260:Female; D007004:Hypoglycemic Agents; D020738:Leptin / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha
chemical_list: D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007004:Hypoglycemic Agents; D020738:Leptin; D008070:Lipopolysaccharides; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D003907:Dexamethasone
references.citation: Diabetes. 1997 Mar;46(3):342-7
references.pmid: 9032087
references.citation: Mol Cell Endocrinol. 2002 Nov 29;197(1-2):221-9
references.pmid: 12431816
references.citation: Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E731-40
references.pmid: 15562246
references.citation: Biochem Biophys Res Commun. 2002 Jan 25;290(3):1084-9
references.pmid: 11798186
references.citation: Int J Obes Relat Metab Disord. 2003 Dec;27 Suppl 3:S25-8
references.pmid: 14704740
references.citation: J Clin Invest. 2003 Dec;112(12):1821-30
references.pmid: 14679177
references.citation: Science. 1993 Jan 1;259(5091):87-91
references.pmid: 7678183
references.citation: Circulation. 1999 Dec 21-28;100(25):2473-6
references.pmid: 10604883
references.citation: Nature. 2006 Dec 14;444(7121):840-6
references.pmid: 17167471
references.citation: J Clin Invest. 1996 Aug 15;98(4):1004-9
references.pmid: 8770873
references.citation: Int J Obes (Lond). 2008 Dec;32 Suppl 7:S52-4
references.pmid: 19136991
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7265-70
references.pmid: 12756299
references.citation: Nature. 2006 Dec 14;444(7121):860-7
references.pmid: 17167474
references.citation: Diabetes. 1997 Dec;46(12):1939-44
references.pmid: 9392477
references.citation: Horm Metab Res. 2008 Dec;40(12):861-8
references.pmid: 18792883
references.citation: Diabetes. 1998 Sep;47(9):1384-91
references.pmid: 9726225
references.citation: J Nutr. 1998 Dec;128(12 Suppl):2771S-2775S
references.pmid: 9868263
references.citation: Biochem Biophys Res Commun. 2004 May 21;318(1):168-75
references.pmid: 15110769
references.citation: J Biol Chem. 2003 Nov 14;278(46):45777-84
references.pmid: 12952969
references.citation: J Biol Chem. 2000 Aug 11;275(32):24255-63
references.pmid: 10823826
references.citation: J Clin Endocrinol Metab. 1997 Aug;82(8):2542-7
references.pmid: 9253331
references.citation: Trends Endocrinol Metab. 2006 Oct;17(8):314-20
references.pmid: 16938460
references.citation: Mol Cell Endocrinol. 2000 Jan 25;159(1-2):79-88
references.pmid: 10687854
references.citation: Horm Metab Res. 2005 Aug;37(8):474-81
references.pmid: 16138259
references.citation: J Biol Chem. 1995 Jul 7;270(27):15958-61
references.pmid: 7608151
references.citation: Proc Nutr Soc. 2001 Aug;60(3):329-39
references.pmid: 11681807
references.citation: Nature. 2005 Dec 8;438(7069):803-19
references.pmid: 16341006
references.citation: Endocrinology. 2003 Sep;144(9):3765-73
references.pmid: 12933646
references.citation: Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E331-9
references.pmid: 15100092
references.citation: Vet Clin Pathol. 2009 Jun;38(2):136-56
references.pmid: 19392760
references.citation: Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E941-9
references.pmid: 14749206
references.citation: J Clin Invest. 1997 Dec 1;100(11):2777-82
references.pmid: 9389742
references.citation: Pflugers Arch. 2006 Jul;452(4):418-27
references.pmid: 16586095
references.citation: J Vet Med Sci. 2001 Jan;63(1):17-23
references.pmid: 11217057
references.citation: Obes Res. 2005 Apr;13(4):662-9
references.pmid: 15897474
references.citation: Am J Vet Res. 2007 Jan;68(1):57-62
references.pmid: 17199419
references.citation: Br J Nutr. 2004 Sep;92(3):347-55
references.pmid: 15469638
references.citation: J Clin Endocrinol Metab. 2002 Dec;87(12):5662-7
references.pmid: 12466369
references.citation: Int J Obes Relat Metab Disord. 2003 Dec;27 Suppl 3:S41-5
references.pmid: 14704743
references.citation: J Nutr. 2006 Jul;136(7 Suppl):1940S-1946S
references.pmid: 16772464
references.citation: Diabetes. 2005 Aug;54(8):2460-70
references.pmid: 16046315
references.citation: Nat Med. 2001 Aug;7(8):947-53
references.pmid: 11479628
references.citation: Obes Rev. 2008 Jan;9(1):20-9
references.pmid: 17956545
references.citation: J Clin Invest. 2006 Jun;116(6):1494-505
references.pmid: 16691291
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Res Vet Sci. 2006 Apr;80(2):127-32
references.pmid: 16051287
references.citation: J Lipid Res. 2007 Sep;48(9):1905-14
references.pmid: 17699733
references.citation: Nature. 2006 Dec 14;444(7121):847-53
references.pmid: 17167472
references.citation: Eur J Endocrinol. 1996 Nov;135(5):619-25
references.pmid: 8980166
references.citation: Nat Med. 2001 Aug;7(8):941-6
references.pmid: 11479627
references.citation: Science. 2003 Sep 26;301(5641):1898-903
references.pmid: 14512627
references.citation: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5793-6
references.pmid: 8650171
references.citation: Circulation. 2000 Sep 12;102(11):1296-301
references.pmid: 10982546
references.citation: Domest Anim Endocrinol. 2009 Nov;37(4):214-26
references.pmid: 19674864
references.citation: J Clin Invest. 2003 Dec;112(12):1796-808
references.pmid: 14679176