MAFB as a novel regulator of human adipose tissue inflammation

Abstract

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.

Effects of milk product intake on thigh muscle strength and NFKB gene methylation during home-based interval walking training in older women: A randomized, controlled pilot study

“…Enhanced hyper-methylation of these genes by post-exercise milk product intake may suppress MAP kinase signaling, as well as NF-κB signaling pathways [53–56]. On the other hand, enhanced hypo-methylation of MYC by post-exercise milk product intake (Fig 6) may be a reaction to the aforementioned hyper-methylation to balance the inflammatory response [57, 58].…”

Transcription Factor MafB Promotes Hepatocellular Carcinoma Cell Proliferation through Up-Regulation of Cyclin D1

“…Previous studies have shown that tumor necrosis factor (TNF) α, a proinflammatory cytokine, increased MafB expression in human monocytic cells and primary adipocytes [7,9,13]. Besides, Borrelli et al identified MafB as a direct transcriptional target of C/EBPδ in human primary keratinocytes by ChIP on chip assays [14].…”

“…Initially, MafB was shown to form heterodimers with v-Maf and Fos through its zipper structure and induced transformation of chicken embryo fibroblasts in vitro [5]. Subsequent studies found that MafB played an important role in the regulation of pancreatic alpha cell, beta cell, osteoclast, macrophage and adipocyte differentiation [6][7][8][9][10]. Besides, MafB was viewed as a highly sensitive and specific marker for poor prognosis in multiple myeloma patients [11].…”

MafB deficiency accelerates the development of obesity in mice

“…Our previous study showed human MAFB and AIM were coexpressed in atherosclerosis lesion of patient [9]. In addition, a recent study showed that human MAFB is expressed in ATMs and MAFB expression correlates negatively with lipogenesis and lipolysis in human adipocytes [28]. These evidence suggest that MAFB may regulate AIM expression in human ATMs because AIM also inhibits fatty acid synthase activity of adipocyte [16].…”