Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue

• Published in: American journal of physiology: endocrinology and metabolism 2006-12, Vol.291 (6), p.E1264-E1273
• Main Authors: Warne, James P, John, Christopher D, Christian, Helen C, Morris, John F, Flower, Roderick J, Sugden, David, Solito, Egle, Gillies, Glenda E, Buckingham, Julia C
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Adipocytes - ultrastructure; Adipose Tissue - metabolism; Adrenergic beta-Agonists - pharmacology; Animals; Annexin A1 - genetics; Annexin A1 - physiology; Blotting, Western; Body Weight - physiology; Catecholamines - pharmacology; Catecholamines - physiology; Cell Separation; Cell Size; Cyclic AMP - metabolism; Dexamethasone - pharmacology; Electrophoresis, Polyacrylamide Gel; Epididymis - metabolism; Fatty acids; Gene Deletion; Genes; Interleukin-6 - metabolism; Isoproterenol - pharmacology; Kindergarten; Lipolysis - physiology; Lipopolysaccharides - pharmacology; Male; Mice; Mice, Knockout; Muscle, Smooth, Vascular - cytology; Organ Size - physiology; Reverse Transcriptase Polymerase Chain Reaction; Stromal Cells - physiology; Studies; Tissues
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00655.2005

Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, London; 1 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford; 2 Department of Biochemical Pharmacology, The William Harvey Research Institute, London; and 3 Division of Reproduction and Endocrinology, Kings College London, London, United Kingdom Submitted 29 December 2005 ; accepted in final form 7 July 2006 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 -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. glucocorticoids; adipocytes; catecholamines Address for reprint requests and other correspondence: J. Buckingham, Dept. of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK (e-mail: j.buckingham{at}imperial.ac.uk )