Induction of STEAP4 correlates with 1,25‐dihydroxyvitamin D₃ stimulation of adipogenesis in mesenchymal progenitor cells derived from human adipose tissue

Abstract

The vitamin D receptor (VDR) is expressed in human adipocytes and is transiently induced during early adipogenesis in mesenchymal progenitor cell models. VDR null mice exhibit enhanced energy expenditure and reduced adiposity even when fed high fat diets. Adipocyte-specific transgenic-expression of human VDR in mice enhances adipose tissue mass, indicating that VDR activation in adipocytes enhances lipid storage in vivo. In these studies, we conducted genomic profiling and differentiation assays in primary cultures of human adipose-derived mesenchymal progenitor cells to define the role of the VDR and its ligand 1,25-dihydroxyvitamin D3 (1,25D) in adipogenesis. In the presence of adipogenic media, 1,25D promoted lipid accumulation and enhanced the expression of FABP4, FASN, and PPARγ. Mesenchymal cells derived from 6-month old VDR null mice exhibited impaired adipogenesis ex vivo but differentiation was restored by stable expression of human VDR. STEAP4, a gene that encodes a metalloreductase linked to obesity, insulin sensitivity, metabolic homeostasis and inflammation, was highly induced in human adipose cells differentiated in the presence of 1,25D but was minimally affected by 1,25D in undifferentiated precursors. These studies provide a molecular basis for recent epidemiological associations between vitamin D status, body weight and insulin resistance which may have relevance for prevention or treatment of metabolic syndrome and obesity.

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“…Several studies have shown that STAMP2 expression is greatly induced upon adipocyte differentiation in vitro [18][19][20][21][27][28][29]. We have recently also shown that murine Stamp1 and Stamp3 mRNA expression is regulated in 3T3-L1 cells upon their adipogenic conversion [20].…”

“…STAMP2, also known as STEAP4 and tumor necrosis factor-α-induced adipose-related protein (TIARP), is up-regulated by several pro-inflammatory cytokines in both murine and human metabolic tissue [18][19][20][21][22][23][24][25][26]. In addition, STAMP2 expression is induced during adipocyte differentiation [18][19][20][21][27][28][29]. Furthermore, in vitro suppression of Stamp2 expression in 3T3-L1 cells inhibits adipogenesis [20].…”

Role or Synergistic Interaction of Adenosine and Vitamin D3 Alongside High-Intensity Interval Training and Isocaloric Moderate Intensity Training on Metabolic Parameters: Protocol for an Experimental Study (Preprint)

“…On the other hand, while some studies have shown that the adipogenesis [24,25] continues through different mechanisms, others have focused on identifying intervention factors that can lead to weight loss, particularly, fat weight. The researchers, revealing the undetected effects of molecules driven from ATP, ADP and AMP called adenosine [26].…”

Genetic Variants in Six-Transmembrane Epithelial Antigen of Prostate 4 Increase Risk of Developing Metabolic Syndrome in a Han Chinese Population

“…STEAP4 plays an important role in various functions of the human body, such as adipocyte development, metabolism, adipocyte differentiation, insulin sensitivity, and metabolic homeostasis (Zhang et al, 2008;Guo et al, 2011;Narvaez et al, 2013;Matsumoto et al, 2014). An altered expression of STEAP4 was linked with a cluster of metabolic abnormalities, such as obesity, insulin insensitivity, metabolic homeostasis, and inflammation (Chen et al, 2014).…”

“…The expression of STEAP4 could be regulated by a variety of inflammatory cytokines, hormones, or adipokines, such as TNFa, IL-6, IL-1b, and leptin in adipocytes (Kralisch et al, 2009;Chen et al, 2010;Tanaka et al, 2012). In addition, recent studies have proved that STEAP4 plays an important role in the pathogenesis of MetS: STEAP4 primarily enhances the expression of 1,25-dihydroxy vitamin D 3 , CCAAT/enhancer binding protein alpha (C/EBPa), and peroxisome proliferator-activated receptor gamma (PPAR-c)-stimulated adipogenesis (Narvaez et al, 2013;Sikkeland and Saatcioglu, 2013). All these observations indicate that STEAP4 may be contributing to the development of MetS.…”