Differential function of Akt1 and Akt2 in human adipocytes

Fischer‐Posovszky, Pamela; Tews, Daniel; Horenburg, Sina; Debatin, Klaus‐Michael; Wabitsch, Martin

doi:10.1016/j.mce.2012.03.018

Cited by 48 publications

(35 citation statements)

References 40 publications

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“…The Akt1 isoform has been shown to be essential in the regulation of development and growth (26,32). In contrast, the Akt2 isoform is mostly involved in glucose uptake (33) and adipogenesis (34). These actions have lead several investigators to study the involvement of Akt2 in metabolic diseases, such as diabetes and obesity (33).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Stechschulte

Wuescher

Marino

et al. 2014

Journal of Biological Chemistry

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Background:The glucocorticoid receptor ␤ (GR␤) is a positive regulator of growth. Results: GR␤ suppression of PTEN resulted in enhanced phosphorylation of Akt and growth. Conclusion: GR␤ enhances insulin-induced proliferation by suppressing PTEN and activating Akt1. Significance: GR␤ suppression of PTEN indicates that it has an important role in growth factor signaling and potentially cancer.

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Section: Discussionmentioning

confidence: 99%

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Stechschulte

Wuescher

Marino

et al. 2014

Journal of Biological Chemistry

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“…Akt signaling is indispensable for the regulation of preadipocyte and adipocyte number. It is also important for the regulation of insulin-stimulated metabolic pathways in human adipocytes (24). Furthermore, it has been reported that phosphorylation of Akt reduces the expression of forkhead transcriptional factor 1 (Foxo1), which is an antagonist of PPAR-γ, thus enhancing the expression of PPAR-γ indirectly and promoting adipogenesis (25,26).…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Yang

Ren

Song

et al. 2013

International Journal of Molecular Medicine

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Abstract. Glucagon-like peptide 1 (GLP-1), a gut-derived peptide, has been reported to have profound effects on metabolism and to reduce insulin resistance. Adipocyte hyperplasia stimulated by preadipocyte differentiation has a positive effect on adipose tissue insulin sensitivity. However, it remains less clear whether GLP-1 plays a role in adipogenesis. In this study, we examined the effect of GLP-1 on preadipocyte differentiation and investigated the mechanisms that may be involved in this effect. In our 3T3-L1 cell study, we tested the levels of adipocyte-specific markers and signaling pathways during preadipocyte differentiation. In addition, Oil Red O staining was used to examine lipid accumulation. Image Pro Plus 5.02 was used to analyze the size and number of lipid droplets. We found that GLP-1 elevated the protein expression levels of free fatty acid-binding protein 4 (aP2) and the transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) in a dose-dependent manner during 3T3-L1 preadipocyte differentiation. Furthermore, RT-PCR results showed that GLP-1 promoted CCAAT/enhancer-binding protein α (C/EBPα) and lipoprotein lipase (LPL) expression at the transcriptional level. These data suggest that GLP-1 promotes preadipocyte differentiation. Our study also found that treatment of the cells with 100 nM GLP-1 enhanced the phosphorylation of Akt signaling during the first 24 h of differentiation. Although Oil Red O staining showed that GLP-1 had no significant effect on lipid accumulation, there were increased numbers of small adipocytes in the cells treated with 100 nM GLP-1. Taken together, these results indicate that GLP-1 regulates 3T3-L1 adipogenesis and the Akt signaling pathway may be involved in this process. The differentiated small adipocytes may have a positive effect against insulin resistance and obesity. IntroductionThe growing prevalence of obesity constitutes a major health problem worldwide (1). Obesity, particularly abdominal obesity, has a strong relationship with insulin resistance and is a major risk factor for type 2 diabetes and cardiovascular disease (2,3). The imbalance between energy intake and expenditure contributes to the development of obesity (1,4); the cellular mechanisms for which include the expansion of white adipose tissue via the hypertrophy of preexisting adipocytes and hyperplasia resulting from the adipogenesis of preadipocytes (4,5). When animals are maintained on a highfat diet, adipo cyte cell size initially increases, followed by an increase in fat cell number upon prolonged over-nutrition (6). In adults, ~10% of fat cells are renewed from preadipocytes annually (7). One study in adults demonstrated that short-term overfeeding increases the adipocyte cell numbers (8). Thus, adipogenesis probably has a role in the pathology of obesity in human adults. However, there are significant differences in lipid and glucose metabolism between adipocyte hypertrophy and hyperplasia (9-11). Recent studies have shown that adipocyte hypertrophy is negatively corre...

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“…Since CoPPIX, the HO-1 activator, increased the activity of Akt in adipocytes of obese mice (27), it was postulated that HO-1 affects development of adipose tissue in vivo in rats through modulation of Aktdependent pathways (192). However, as Akt kinase is rather regarded as a positive stimulator of adipogenesis (39,55,167), the mechanism of antiadipogenic effects of HO-1 involves probably also other pathways and needs further elucidation.…”

Section: Ho-1 Affects Differentiationmentioning

confidence: 99%

Role of Heme Oxygenase-1 in Postnatal Differentiation of Stem Cells: A Possible Cross-Talk with MicroRNAs

Kozakowska

Szade

Dulak

et al. 2014

Antioxidants & Redox Signaling

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Significance: Heme oxygenase-1 (HO-1) converts heme to biliverdin, carbon monoxide, and ferrous ions, but its cellular functions are far beyond heme metabolism. HO-1 via heme removal and degradation products acts as a cytoprotective, anti-inflammatory, immunomodulatory, and proangiogenic protein, regulating also a cell cycle. Additionally, HO-1 can translocate to nucleus and regulate transcription factors, so it can also act independently of enzymatic function. Recent Advances: Recently, a body of evidence has emerged indicating a role for HO-1 in postnatal differentiation of stem and progenitor cells. Maturation of satellite cells, skeletal myoblasts, adipocytes, and osteoclasts is inhibited by HO-1, whereas neurogenic differentiation and formation of cardiomyocytes perhaps can be enhanced. Moreover, HO-1 influences a lineage commitment in pluripotent stem cells and maturation of hematopoietic cells. It may play a role in development of osteoblasts, but descriptions of its exact effects are inconsistent. Critical Issues: In this review we discuss a role of HO-1 in cell differentiation, and possible HO-1-dependent signal transduction pathways. Among the potential mediators, we focused on microRNA (miRNA). These small, noncoding RNAs are critical for cell differentiation. Recently we have found that HO-1 not only influences expression of specific miRNAs but also regulates miRNA processing enzymes. Future Directions: It seems that interplay between HO-1 and miRNAs may be important in regulating fates of stem and progenitor cells and needs further intensive studies.

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Differential function of Akt1 and Akt2 in human adipocytes

Cited by 48 publications

References 40 publications

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Role of Heme Oxygenase-1 in Postnatal Differentiation of Stem Cells: A Possible Cross-Talk with MicroRNAs

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