scholarly journals Serum- and Glucocorticoid-Inducible Kinase 1 (SGK1) Regulates Adipocyte Differentiation via Forkhead Box O1

2010 ◽  
Vol 24 (2) ◽  
pp. 370-380 ◽  
Author(s):  
Natalia Di Pietro ◽  
Valentine Panel ◽  
Schantel Hayes ◽  
Alessia Bagattin ◽  
Sunitha Meruvu ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Mesenchymal Precursor Cells ◽  
And Function

Abstract The serum and glucocorticoid-inducible kinase 1 (SGK1) is an inducible kinase the physiological function of which has been characterized primarily in the kidney. Here we show that SGK1 is expressed in white adipose tissue and that its levels are induced in the conversion of preadipocytes into fat cells. Adipocyte differentiation is significantly diminished via small interfering RNA inhibition of endogenous SGK1 expression, whereas ectopic expression of SGK1 in mesenchymal precursor cells promotes adipogenesis. The SGK1-mediated phenotypic effects on differentiation parallel changes in the mRNA levels for critical regulators and markers of adipogenesis, such as peroxisome proliferator-activated receptor γ, CCAAT enhancer binding protein α, and fatty acid binding protein aP2. We demonstrate that SGK1 affects differentiation by direct phosphorylation of Foxo1, thereby changing its cellular localization from the nucleus to the cytosol. In addition we show that SGK1−/− cells are unable to relocalize Foxo1 to the cytosol in response to dexamethasone. Together these results show that SGK1 influences adipocyte differentiation by regulating Foxo1 phosphorylation and reveal a potentially important function for this kinase in the control of fat mass and function.

scholarly journals Novel Function of α-Cubebenoate Derived from Schisandra chinensis as Lipogenesis Inhibitor, Lipolysis Stimulator and Inflammasome Suppressor

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4995
Author(s):  
Su Ji Bae ◽  
Ji Eun Kim ◽  
Yun Ju Choi ◽  
Su Jin Lee ◽  
Jeong Eun Gong ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Binding Protein ◽  
Fatty Acid Synthetase ◽  
Inflammasome Activation ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Schisandra Chinensis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Ppar Γ

The efficacy of α-cubebenoate isolated from Schisandra chinensis has been previously studied in three disease areas, namely inflammation, sepsis, and allergy, and its role in other diseases is still being explored. To identify the novel function of α-cubebenoate on lipid metabolism and related inflammatory response, alterations in fat accumulation, lipogenesis, lipolysis, and inflammasome activation were measured in 3T3-L1 preadipocytes and primary adipocytes treated with α-cubebenoate. Lipid accumulation significantly decreased in MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-stimulated 3T3-L1 adipocytes treated with α-cubebenoate without any significant cytotoxicity. The mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT-enhancer binding protein (C/EBP) α for adipogenesis, as well as adipocyte fatty acid binding protein 2 (aP2) and fatty acid synthetase (FAS) for lipogenesis, were reduced after α-cubebenoate treatment, while cell cycle arrest at G2/M stage was restored in the same group. α-cubebenoate treatment induced glycerol release in primary adipocytes and enhanced expression of lipolytic proteins (HSL, perilipin, and ATGL) expression in MDI-stimulated 3T3-L1 adipocytes. Inflammasome activation and downstream cytokines expression were suppressed with α-cubebenoate treatment, but the expression of insulin receptor signaling factors was remarkably increased by α-cubebenoate treatment in MDI-stimulated 3T3-L1 adipocytes. These results indicate that α-cubebenoate may play a novel role as lipogenesis inhibitor, lipolysis stimulator, and inflammasome suppressor in MDI-stimulated 3T3-L1 adipocytes. Our results provide the possibility that α-cubebenoate can be considered as one of the candidates for obesity management.

scholarly journals MIR221HG Is a Novel Long Noncoding RNA that Inhibits Bovine Adipocyte Differentiation

Genes ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 29 ◽  
Author(s):  
Mingxun Li ◽  
Qisong Gao ◽  
Zhichen Tian ◽  
Xubin Lu ◽  
Yujia Sun ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Bioinformatics Analyses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Consensus Sequences ◽  
Rapid Amplification

Adipogenesis is a complicated but precisely orchestrated process mediated by a series of transcription factors. Our previous study has identified a novel long noncoding RNA (lncRNA) that was differentially expressed during bovine adipocyte differentiation. Because this lncRNA overlaps with miR-221 in the genome, it was named miR-221 host gene (MIR221HG). The purpose of this study was to clone the full length of MIR221HG, detect its subcellular localization, and determine the effects of MIR221HG on bovine adipocyte differentiation. The 5′ rapid amplification of cDNA ends (RACE) and 3′ RACE analyses demonstrated that MIR221HG is a transcript of 1064 nucleotides, is located on the bovine X chromosome, and contains a single exon. Bioinformatics analyses suggested that MIR221HG is an lncRNA and the promoter of MIR221HG includes the binding consensus sequences of the forkhead box C1 (FOXC1) and krüppel-like factor5 (KLF5). The semi-quantitative PCR and quantitative real-time PCR (qRT-PCR) of nuclear and cytoplasmic fractions revealed that MIR221HG mainly resides in the nucleus. Inhibition of MIR221HG significantly increased adipocyte differentiation, as indicated by a dramatic increment in the number of mature adipocytes and in the expression of the respective adipogenic markers, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and fatty acid binding protein 4 (FABP4). Our results provide a basis for elucidating the mechanism by which MIR221HG regulates adipocyte differentiation.

scholarly journals Statin Induction of Liver Fatty Acid-Binding Protein (L-FABP) Gene Expression Is Peroxisome Proliferator-activated Receptor-α-dependent

2004 ◽  
Vol 279 (44) ◽  
pp. 45512-45518 ◽  
Author(s):  
Jean-François Landrier ◽  
Charles Thomas ◽  
Jacques Grober ◽  
Hélène Duez ◽  
Frédéric Percevault ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Statin Treatment ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Responsive Element

Statins are drugs widely used in humans to treat hypercholesterolemia. Statins act by inhibiting cholesterol synthesis resulting in the activation of the transcription factor sterol-responsive element-binding protein-2 that controls the expression of genes involved in cholesterol homeostasis. Statin therapy also decreases plasma triglyceride and non-esterified fatty acid levels, but the mechanism behind this effect remains more elusive. Liver fatty acid-binding protein (L-FABP) plays a role in the influx of long-chain fatty acids into hepatocytes. Here we show that L-FABP is a target for statins. In rat hepatocytes, simvastatin treatment induced L-FABP mRNA levels in a dose-dependent manner. Moreover, L-FABP promoter activity was induced by statin treatment. Progressive 5′-deletion analysis revealed that the peroxisome proliferator-activated receptor (PPAR)-responsive element located at position –67/–55 was responsible for the statin-mediated transactivation of the rat L-FABP promoter. Moreover, treatment with simvastatin and the PPARα agonist Wy14,649 resulted in a synergistic induction of L-FABP expression (mRNA and protein) in rat Fao hepatoma cells. This effect was also observedin vivoin wild-type mice but not in PPARα-null animals demonstrating the direct implication of PPARα in L-FABP regulation by statin treatment. Statin treatment resulted in a rise in PPARα mRNA levels bothin vitroandin vivoand activated the mouse PPARα promoter in a reporter assay. Altogether, these data demonstrate that L-FABP expression is up-regulated by statins through a mechanism involving PPARα. Moreover, PPARα might be a statin target gene. These effects might contribute to the triglyceride/non-esterified fatty acid-lowering properties of statins.

scholarly journals Klotho Protein Promotes Adipocyte Differentiation

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3835-3842 ◽  
Author(s):  
Yukana Chihara ◽  
Hiromi Rakugi ◽  
Kazuhiko Ishikawa ◽  
Masashi Ikushima ◽  
Yoshihiro Maekawa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
Early Period ◽  
Peroxisome Proliferator ◽  
Differentiation Markers ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Age Related ◽  
Klotho Protein

Mice with homozygous disruption of the klotho exhibit multiple age-related disorders and have barely detectable amounts of white adipose tissue. Although klotho expression in cultured adipocytes has been reported, little is known about its function in adipocytes. In the present study, we investigated the role of klotho on adipocyte differentiation. Adipocyte differentiation was induced by incubation of confluent 3T3-L1 cells with insulin, dexamethasone, and 1-methyl-3-isobutyl-xanthin. Klotho-siRNA and expression vector were produced for klotho suppression and overexpression, respectively. Klotho protein was purified for determination of the hormonal effect of klotho. Klotho mRNA and protein expression increased up to the 3rd d of differentiation. A peroxisome proliferator-activated receptor-γ agonist increased klotho expression during the early period of adipocyte differentiation. The mRNA expression of adipocyte differentiation markers, such as CCAAT/enhancer-binding protein (C/EBP)α, C/EBPβ, C/EBPδ, peroxisome proliferator-activated receptor-γ, and fatty acid binding protein 4, was decreased by klotho suppression, and increased 1.9- to 3.8-fold by klotho overexpression. The results of Oil Red O staining also suggested that klotho overexpression promoted adipocyte differentiation. Klotho protein stimulation resulted in a 2.4- to 4.6-fold increase in mRNA expression of differentiation markers compared with control, and the time course depended on adipocyte induction status. Western blot analysis showed that protein levels of C/EBPα and C/EBPδ were increased by Klotho protein stimulation. These results suggest that klotho works as a hormonal factor to promote adipocyte differentiation in the early days, during the period of transient proliferation in the differentiation process, and that klotho may play an essential role in adipocyte differentiation.

scholarly journals Traditional Herbal Formula Oyaksungi-San Inhibits Adipogenesis in 3T3-L1 Adipocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sae-Rom Yoo ◽  
Chang-Seob Seo ◽  
Hyeun-Kyoo Shin ◽  
Soo-Jin Jeong
Keyword(s):  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Herbal Formula ◽  
Related Factors ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Gpdh Activity ◽  
Protein Levels ◽  
Intracellular Lipid Accumulation ◽  
Glycerol 3 Phosphate Dehydrogenase

Background. Oyaksungi-san (OYSGS) is a herbal formula that has been used for treating cardiovascular diseases in traditional Asian medicine. Here, we investigated the antiadipogenic effect of OYSGS extract in 3T3-L1 adipose cells.Methods. 3T3-L1 preadipocytes were differentiated into adipocytes with or without OYSGS. After differentiation, we measured Oil Red O staining, glycerol-3-phosphate dehydrogenase (GPDH) activity, leptin production, mRNA, and protein levels of adipogenesis-related factors.Results. OYSGS extract dramatically inhibited intracellular lipid accumulation in the differentiated adipocytes. It also significantly suppressed the (GPDH) activity, triglyceride (TG) content, and leptin production by reducing the expression of adipogenesis-related genes including lipoprotein lipase, fatty acid binding protein 4, CCAAT/enhancer-binding protein-alpha (C/EBP-α), and peroxisome proliferator-activated receptor gamma (PPAR-γ). Furthermore, OYSGS clearly enhanced phosphorylation of AMP-activated protein kinase (AMPK) as well as its substrate acetyl CoA (ACC) carboxylase.Conclusions. Our results demonstrate that OYSGS negatively controls TG accumulation in 3T3-L1 adipocytes. We suggest antiadipogenic activity of OYSGS and its potential benefit in preventing obesity.

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