Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue.
In this study, epididymal adipose tissue from male annexin 1 (ANXA1)-null and wild-type control mice were used to explore the potential role of ANXA1 in adipocyte biology. ANXA1 was detected by Western blot analysis in wild-type tissue and localized predominantly to the stromal-vascular compartment. Epididymal fat pad mass was reduced by ANXA1 gene deletion, but adipocyte size was unchanged, suggesting that ANXA1 is required for the maintenance of adipocyte and/or preadipocyte cell number. Epididymal tissue from wild-type mice responded in vitro to noradrenaline and isoprenaline with increased glycerol release, reduced IL-6 release, and increased cAMP accumulation. Qualitatively similar but significantly attenuated responses to the catecholamines were observed in tissue from ANXA1-null mice, an effect that was not associated with changes in beta-adrenoceptor mRNA expression. Lipopolysaccharide (LPS) also stimulated lipolysis in vitro, but its effects were muted by ANXA1 gene deletion. By contrast, LPS failed to influence IL-6 release from wild-type tissue but stimulated the release of the cytokine from tissue from ANXA1-null mice. ANXA1 gene deletion did not affect glucocorticoid receptor expression or the ability of dexamethasone to suppress catecholamine-induced lipolysis. It did, however, augment IL-6 expression and modify the inhibitory effects of glucocorticoids on IL-6 release. Collectively, these studies suggest that ANXA1 supports aspects of adipose tissue mass and alters the sensitivity of epididymal adipose tissue to catecholamines, glucocorticoids, and LPS, thereby modulating lipolysis and IL-6 release.
Warne
James P
JP
Dept. of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Campus, London, W12 0NN, UK.
John
Christopher D
CD
Christian
Helen C
HC
Morris
John F
JF
Flower
Roderick J
RJ
Sugden
David
D
Solito
Egle
E
Gillies
Glenda E
GE
Buckingham
Julia C
JC
D017667:Adipocytes / Q000378:metabolism / Q000648:ultrastructure; D000273:Adipose Tissue / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017305:Annexin A1 / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D002395:Catecholamines / Q000494:pharmacology / Q000502:physiology; D002469:Cell Separation; D048429:Cell Size; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004822:Epididymis / Q000378:metabolism*; D017353:Gene Deletion; D015850:Interleukin-6 / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009929:Organ Size / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology
D000318:Adrenergic beta-Agonists; D017305:Annexin A1; D002395:Catecholamines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D003907:Dexamethasone; D000242:Cyclic AMP; D007545:Isoproterenol