SLC39A14, a LZT protein, is induced in adipogenesis and transports zinc (original) (raw)
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Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways
International Journal of Molecular Sciences
The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte co...
Understanding Adipocyte Differentiation
Physiological Reviews, 1998
Gregoire, Francine M., Cynthia M. Smas, and Hei Sook Sul. Understanding Adipocyte Differentiation. Physiol. Rev. 78: 783–809, 1998. — The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extensively studied using preadipocyte culture systems. Committed preadipocytes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional ...
Journal of Biological Chemistry, 2007
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is expressed in adipocytes and is proposed to be involved in the regulation of glucose tolerance and atherosclerosis in type 2 diabetes, because L-PGDS gene knockout mice show abnormalities in these functions. However, the role of L-PGDS and the regulation mechanism governing its gene expression in adipocytes remain unclear. Here, we applied small interference RNA of L-PGDS to mouse 3T3-L1 cells and found that it suppressed differentiation of these cells into adipocytes. Reporter analysis of the mouse L-PGDS promoter demonstrated that a responsive element for liver receptor homolog-1 (LRH-1) at ؊233 plays a critical role in preadipocytic 3T3-L1 cells. Moreover, we identified two sterol regulatory elements (SREs) at ؊194 to be ciselements for activation of L-PGDS gene expression in adipocytic 3T3-L1 cells. L-PGDS mRNA was induced in response to synthetic liver X receptor agonist, T0901317, through activation of the expression of SRE-binding protein-1c (SREBP-1c) in the adipocytic 3T3-L1 cells. The results of electrophoretic mobility shift assay and chromatin immunoprecipitation assay revealed that LRH-1 and SREBP-1c bound to their respective binding elements in the promoter of L-PGDS gene. Small interference RNA-mediated suppression of LRH-1 or SREBP-1c decreased L-PGDS gene expression in preadipocytic or adipocytic 3T3-L1 cells, respectively. These results indicate that L-PGDS gene expression is activated by LRH-1 in preadipocytes and by SREBP-1c in adipocytes. Liver X receptor-mediated up-regulation of L-PGDS through activation of SREBP-1c is a novel pathway to enhance adipocyte differentiation.
Endocrinology, 2002
PPAR␥ is an adipocyte-specific nuclear hormone receptor. Agonists of PPAR␥, such as thiazolidinediones (TZDs), promote adipocyte differentiation and have insulin-sensitizing effects in animals and diabetic patients. Affymetrix oligonucleotide arrays representing 6347 genes were employed to profile the gene expression responses of mature 3T3-L1 adipocytes and differentiating preadipocytes to a TZD PPAR␥ agonist in vitro. The expression of 579 genes was significantly up-or down-regulated by more than 1.5-fold during differentiation and/or by treatment with TZD, and these genes were organized into 32 clusters that demonstrated concerted changes in expression of genes controlling cell growth or lipid metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of -catenin as a new PPAR␥ target gene. Both mRNA and protein levels for -catenin were down-regulated in 3T3-L1 adipocytes compared with fibroblasts and were further decreased by treatment of adipocytes with PPAR␥ agonists. Treatment of db/db mice with a PPAR␥ agonist also resulted in reduction of -catenin mRNA levels in adipose tissue. These results suggest that -catenin plays an important role in the regulation of adipogenesis. Thus, the transcriptional patterns revealed in this study further the understanding of adipogenesis process and the function of PPAR␥ activation.
Endocrinology, 2002
PPAR␥ is an adipocyte-specific nuclear hormone receptor. Agonists of PPAR␥, such as thiazolidinediones (TZDs), promote adipocyte differentiation and have insulin-sensitizing effects in animals and diabetic patients. Affymetrix oligonucleotide arrays representing 6347 genes were employed to profile the gene expression responses of mature 3T3-L1 adipocytes and differentiating preadipocytes to a TZD PPAR␥ agonist in vitro. The expression of 579 genes was significantly up-or down-regulated by more than 1.5-fold during differentiation and/or by treatment with TZD, and these genes were organized into 32 clusters that demonstrated concerted changes in expression of genes controlling cell growth or lipid metabolism. Quantitative PCR was employed to further characterize gene expression and led to the identification of -catenin as a new PPAR␥ target gene. Both mRNA and protein levels for -catenin were down-regulated in 3T3-L1 adipocytes compared with fibroblasts and were further decreased by treatment of adipocytes with PPAR␥ agonists. Treatment of db/db mice with a PPAR␥ agonist also resulted in reduction of -catenin mRNA levels in adipose tissue. These results suggest that -catenin plays an important role in the regulation of adipogenesis. Thus, the transcriptional patterns revealed in this study further the understanding of adipogenesis process and the function of PPAR␥ activation.
Journal of Biological Chemistry, 2002
We evaluated the hypothesis of sterol-regulatory element-binding protein (SREBP)-1c being a general mediator of the transcriptional effects of insulin, with a focus on adipocytes, in which insulin profoundly influences specific gene expression. Using real time quantitative reverse transcriptase-PCR to monitor changes in the expression of about 50 genes that cover a wide range of adipocyte functions, we have compared the impact of insulin treatment with that of adenoviral overexpression of either dominant positive or dominant negative SREBP-1c mutants in 3T3-L1 adipocytes. As expected, insulin up-regulated, dominant positive stimulated, and dominant negative decreased previously characterized direct SREBP targets (FAS, SCD-1, and low density lipoprotein receptor). We also identified three novel SREBP-1c transcriptional targets in adipocytes, which were confirmed by run-on assays: plasminogen activator inhibitor 1, CCAAT/enhancer-binding protein ␦ (C/ EBP␦), and C/EBP. Because most insulin-regulated genes were also modulated by SREBP-1c mutants, our data establish that 1) SREBP-1c is an important mediator of insulin transcriptional effects in adipocytes, and 2) C/EBP is under the direct control of SREBP-1c, as demonstrated by the ability of SREBP-1c to activate the transcription from C/EBP promoter through canonical SREBP binding sites. Thus, some of the effects of insulin and/or SREBP-1c in mature fat cells might require C/EBP or C/EBP␦ as transcriptional relays.