GATA Proteins Work Together with Friend of GATA (FOG) and C-terminal Binding Protein (CTBP) Co-regulators to Control Adipogenesis

Jack, Briony; Crossley, Merlin

doi:10.1074/jbc.m110.141317

Cited by 32 publications

(27 citation statements)

References 42 publications

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“…TFs of GATA binding proteins have been found to serve as negative regulators of adipocyte formation [24,25]. GATA-2, a member of GATA binding protein family, suppresses adipocyte differentiation [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…PPARγ plays key roles in promoting adipocyte differentiation [23] and in inhibiting HSC activation [2]. In contrast, GATA proteins serve as the negative regulators of adipocyte formation [24,25]. Since leptin treatment reduced PPARγ expression in HSCs [14,15], it was interesting to investigate whether GATA proteins bound to the potential GATA protein binding site in PPARγ1 promoter and mediated leptin inhibition of PPARγ1 expression in HSCs.…”

Section: Leptin Response Elements Exist Between Position −2333 and −2mentioning

confidence: 98%

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GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation

Zhou

Guan

Qiao

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Hepatic stellate cell (HSC) activation is a crucial step in the development of liver fibrosis. Peroxisome-proliferator activated receptor γ (PPARγ) exerts a key role in the inhibition of HSC activation. Leptin reduces PPARγ expression in HSCs and plays a unique role in promoting liver fibrosis. The present studies aimed to investigate the mechanisms underlying leptin regulation of PPARγ1 (a major subtype of PPARγ) in HSCs in vivo and in vitro. Results revealed a leptin response region in mouse PPARγ1 promoter and indicated that the region included a GATA binding protein binding site around position -2323. GATA binding protein-2 (GATA-2) could bind to the site and inhibit PPARγ1 promoter activity in HSCs. Leptin induced GATA-2 expression in HSCs in vitro and in vivo. GATA-2 mediated leptin inhibition of PPARγ1 expression by its binding site in PPARγ1 promoter in HSCs and GATA-2 promoted HSC activation. Leptin upregulated GATA-2 expression through β-catenin and sonic hedgehog pathways in HSCs. Leptin-induced increase in GATA-2 was accompanied by the decrease in PPARγ expression in HSCs and by the increase in the activated HSC number and liver fibrosis in vivo. Our data might suggest a possible new explanation for the promotion effect of leptin on liver fibrogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Leptin Response Elements Exist Between Position −2333 and −2mentioning

confidence: 98%

GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation

Zhou

Guan

Qiao

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…However, the finding should be interpreted with caution, since there is a possibility that aberrations in fragile sites are secondary to metabolic stress during clonal expansion. Two other genes were also partly deleted: NEGR1 encodes a protein involved in neurite outgrowth [26,27], and ZFPM2 engaged in hematopoiesis and cardiogenesis [28]. Alterations in these genes have not been specifically reported or probed for in a WT context before, and we can only speculate on the significance of the discovered microdeletions for the development of the tumor investigated in this study.…”

Section: Discussionmentioning

confidence: 91%

High-resolution genomic profiling of an adult Wilms’ tumor: evidence for a pathogenesis distinct from corresponding pediatric tumors

et al. 2011

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Wilms' tumor (WT), the most common kidney tumor among children, is characterized by a triphasic morphology consisting of blastemal, epithelial, and stromal components. Adult WT is a rare malignancy displaying similar histological features. We here present the first published high-resolution genomic analysis of a mixed-type adult WT. This revealed a more pronounced genetic complexity than usually observed in children with mixed-type WT. The majority of chromosomes displayed uniparental disomies, and microdeletions were present in genes with known importance for tumor formation (LRP1B, FHIT, and WWOX) or organogenesis (NEGR1 and ZFPM2), abnormalities not previously reported for pediatric WT. Our results indicate that adult WT is a biological entity distinct from the corresponding pediatric tumor type.

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“…In 3T3-L1 cells, FOG2 is shown to control adipogenesis (15), a key process that determines the mass of adipose tissue. These results are consistent with other studies that showed FOG2 to be an important regulator for development in various tissues (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, FOG2 expression is increased in liver of insulin-resistant mice induced by interleukin-6 injection or with mutation in leptin receptor (db/db) (14). Moreover, overexpression of FOG2 blocks adipogenesis (15), a process closely related to lipid metabolism (16). Although FOG2 expression is not that abundant in normal liver (7,9), hepatic FOG2 may play an important role in the regulation of insulin sensitivity and lipid metabolism.…”

mentioning

confidence: 99%

A Novel Function of Hepatic FOG2 in Insulin Sensitivity and Lipid Metabolism Through PPARα

Guo

Deng

et al. 2016

Diabetes

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Friend of GATA 2 (FOG2) is a transcriptional cofactor involved mostly in cardiac function. The aim of this study was to investigate the role of hepatic FOG2 in insulin sensitivity and lipid accumulation. FOG2 overexpression by adenovirus-expressing FOG2 (Ad-FOG2) significantly attenuates insulin signaling in hepatocytes in vitro. Opposite effects were observed when FOG2 was knocked down through adenovirus-expressing small hairpin RNA for FOG2 (Ad-shFOG2). Furthermore, FOG2 knockdown by Ad-shFOG2 ameliorated insulin resistance in leptin receptor-mutated (db/db) mice, and FOG2 overexpression by Ad-FOG2 attenuated insulin sensitivity in C57BL/6J wild-type (WT) mice. In addition, Ad-FOG2 reduced, whereas Ad-shFOG2 promoted, hepatic triglyceride (TG) accumulation in WT mice under fed or fasted conditions, which was associated with increased or decreased hepatic peroxisome proliferator-activated receptor a (PPARa) expression, respectively. Moreover, the improved insulin sensitivity and increased hepatic TG accumulation by Ad-shFOG2 were largely reversed by adenovirusexpressing PPARa (Ad-PPARa) in WT mice. Finally, we generated FOG2 liver-specific knockout mice and found that they exhibit enhanced insulin sensitivity and elevated hepatic TG accumulation, which were also reversed by AdPPARa. Taken together, the results demonstrate a novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism through PPARa.Insulin resistance is a risk factor for type 2 diabetes (T2D), and dysregulated hepatic lipid metabolism is the major cause of nonalcoholic fatty liver disease. Many studies have demonstrated a relationship between T2D and nonalcoholic fatty liver disease. For example, insulin resistance has been shown to accompany liver steatosis (1-3). On the other hand, improved insulin sensitivity sometimes is not enough to ameliorate disrupted lipid metabolism (4-6). These results suggest a complex relationship between the regulation of insulin sensitivity and hepatic lipid metabolism. Because the liver is critical in the regulation of glucose and lipid metabolism, the function of many genes expressed in the liver needs to be explored.Friend of GATA 2 (FOG2, also known as ZFPM2) was first cloned from mouse embryonic brain (7) and heart (8). FOG2 is expressed in many tissues (8,9) and functions as a coregulator of the transcriptional factor GATA family (7,8). Studies have shown that FOG2 is involved in the regulation of many physiological processes, including coronary vascular development and heart morphology (10-12). However, some studies have implied a possible role of FOG2 in the regulation of insulin signaling and lipid metabolism such that FOG2 can bind to the regulatory unit p85 of phosphatidylinositol 3-kinase (PI3K) and attenuate phosphorylation of protein kinase B (AKT), the major component of insulin signaling in various cell types (13). Furthermore, FOG2 expression is increased in liver of insulin-resistant mice induced by interleukin-6 injection or with mutation in leptin receptor (db/db) (14). Moreover, ...

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GATA Proteins Work Together with Friend of GATA (FOG) and C-terminal Binding Protein (CTBP) Co-regulators to Control Adipogenesis

Abstract: GATA transcription factors have been implicated in controlling adipogenesis in

Cited by 32 publications

References 42 publications

GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation

GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation

High-resolution genomic profiling of an adult Wilms’ tumor: evidence for a pathogenesis distinct from corresponding pediatric tumors

A Novel Function of Hepatic FOG2 in Insulin Sensitivity and Lipid Metabolism Through PPARα

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