MAFB as a novel regulator of human adipose tissue inflammation

• Published in: Diabetologia 2015-09, Vol.58 (9), p.2115-2123
• Main Authors: Pettersson, Annie M. L., Acosta, Juan R., Björk, Christel, Krätzel, Johan, Stenson, Britta, Blomqvist, Lennart, Viguerie, Nathalie, Langin, Dominique, Arner, Peter, Laurencikiene, Jurga
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - cytology; Adipose Tissue, White - metabolism; Adipose Tissue, White - pathology; Body fat; Body Mass Index; Cell culture; Cell Differentiation; Cohort Studies; Diabetes; Fibrosarcoma; Gene expression; Gene Expression Regulation; Human Physiology; Humans; Inflammation; Inflammation - metabolism; Insulin Resistance; Internal Medicine; Lipogenesis; Lipolysis; Macrophages - cytology; MafB Transcription Factor - metabolism; Medicine; Medicine & Public Health; Mesenchymal Stromal Cells - cytology; Metabolic Diseases; Metabolic syndrome; Monocytes - cytology; Obesity; Obesity - metabolism; Proteins; R&D; Regression Analysis; Research & development; Tumor Necrosis Factor-alpha - metabolism; Weight control
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-015-3673-x

Aims/hypothesis Dysregulated expression of metabolic and inflammatory genes is a prominent consequence of obesity causing insulin resistance and type 2 diabetes. Finding causative factors is essential to understanding progression of these pathologies and discovering new therapeutic targets. The transcription factor V-maf musculoaponeurotic fibrosarcoma oncogene homologue B (MAFB) is highly expressed in human white adipose tissue (WAT). However, its role in the regulation of WAT function is elusive. We aimed to characterise MAFB expression and function in human WAT in the context of obesity and insulin resistance. Methods MAFB mRNA expression was evaluated in human WAT from seven cohorts with large inter-individual variation in BMI and metabolic features. Insulin-induced adipocyte lipogenesis and lipolysis were measured and correlated with MAFB expression. MAFB regulation during adipogenesis and the effects of MAFB suppression in human adipocytes was investigated. MAFB regulation by TNF-α was examined in human primary adipocytes and THP-1 monocytes/macrophages. Results MAFB expression in human adipocytes is upregulated during adipogenesis, increases with BMI in WAT, correlates with adverse metabolic features and is decreased after weight loss. MAFB downregulation decreases proinflammatory gene expression in adipocytes and interferes with TNF-α effects. Interestingly, MAFB is differentially regulated by TNF-α in adipocytes (suppressed) and THP-1 cells (upregulated). Further, MAFB is primarily expressed in WAT macrophages/monocytes and its expression correlates with macrophage and inflammatory markers. Conclusions/interpretation Our findings indicate that MAFB is a regulator and a marker of adipose tissue inflammation, a process that subsequently causes insulin resistance.