scholarly journals Glucocorticoids reciprocally regulate expression of the CCAAT/enhancer-binding protein alpha and delta genes in 3T3-L1 adipocytes and white adipose tissue.

1994 ◽  
Vol 269 (29) ◽  
pp. 19041-19047 ◽  
Author(s):  
O.A. MacDougald ◽  
P. Cornelius ◽  
F.T. Lin ◽  
S.S. Chen ◽  
M.D. Lane
2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yea-Jin Park ◽  
Dong-Wook Seo ◽  
Jae-Yun Ju ◽  
Yun-Yeop Cha ◽  
Hyo-Jin An

There has been a remarkable interest in finding lipid inhibitors from natural products to replace synthetic compounds, and a variety of oriental medicinal herbs are reported to have biological activity with regard to lipid inhibition. Buginawa (Bugi) is a novel combined formula that contains twelve medicinal herbs with potential for weight loss induction. We hypothesized that Bugi may have antiobesity effects in 3T3-L1 preadipocytes and in a high-fat diet- (HFD-) induced mouse model. In this study, 3T3-L1 cells were treated with varied concentrations of Bugi (62.5, 125, or 250 μg/mL). Bugi treatment inhibited adipocyte differentiation by suppressing adipogenic transcription genes, including peroxisome proliferator-activated receptor γ protein (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1), and CCAAT/enhancer-binding protein β (C/EBPβ). Mice were fed a normal diet or an HFD for 11 weeks, and Bugi was simultaneously administered at 50 or 100 mg/kg. Bugi administration significantly reduced body weight gain and white adipose tissue (WAT) weight and effectively inhibited lipid droplet accumulation in epididymal white adipose tissue (eWAT) and liver tissue. Further, Bugi treatment suppressed mRNA levels of PPARγ, C/EBPα, and SREBP1 in eWAT and liver tissue. Our findings demonstrate that Bugi could be an effective candidate for preventing obesity and related metabolic disorders.


Diabetes ◽  
2004 ◽  
Vol 53 (11) ◽  
pp. 2757-2766 ◽  
Author(s):  
S.-k. Park ◽  
S.-Y. Oh ◽  
M.-Y. Lee ◽  
S. Yoon ◽  
K.-S. Kim ◽  
...  

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5373-5383 ◽  
Author(s):  
Gabriele Tiller ◽  
Pamela Fischer-Posovszky ◽  
Helmut Laumen ◽  
Andreas Finck ◽  
Thomas Skurk ◽  
...  

Abstract Expansion of adipose tissue mass by hypertrophy and hyperplasia is the hallmark of obesity. An automated cDNA screen was established to identify secreted human proteins with an inhibitory effect on adipocyte differentiation and, thereby, a potential inhibitory effect on adipose tissue growth. A member of the TNF superfamily, TNF-like weak inducer of apoptosis (TWEAK; TNF superfamily 12) was identified by means of high-throughput screening with the lipophilic dye Nile Red as an inhibitor of murine adipocyte differentiation and, subsequently, also of human adipocyte differentiation. TWEAK inhibited lipid deposition in a dose-dependent manner without causing cytotoxic effects. This inhibitory action was mimicked by an agonistic antibody of the TWEAK receptor. The TWEAK receptor (fibroblast growth factor inducible 14; CD266) was expressed on human primary preadipocytes and mature adipocytes. Knockdown of TWEAK receptor by short-hairpin RNA abolished the inhibitory effect of TWEAK on cell differentiation, demonstrating that the effects of TWEAK are mediated by its specific receptor. Inhibition of differentiation was the result of interference at an early step of transcriptional activation as assessed by decreased peroxisome proliferator-activated receptor-γ, CCAAT enhancer-binding protein α (C/EBPα), and CCAAT enhancer-binding protein β (C/EBPβ) mRNA expression. In contrast to TNFα, basal and insulin-stimulated glucose uptake and lipolysis of terminally differentiated mature adipocytes and secretion of proinflammatory cytokines were not altered in the presence of TWEAK, and nuclear factor κ B activity was only weakly induced. We conclude from our findings that TWEAK and the corresponding agonistic antibody have the potential to prevent adipose tissue growth without adversely influencing central metabolic pathways or proinflammatory cytokine secretion in adipose tissue.


2008 ◽  
Vol 22 (9) ◽  
pp. 2049-2060 ◽  
Author(s):  
Shuji Sai ◽  
Cristina L. Esteves ◽  
Val Kelly ◽  
Zoi Michailidou ◽  
Karen Anderson ◽  
...  

Abstract 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inert 11keto-glucocorticoids to active 11β-hydroxy forms, thereby amplifying intracellular glucocorticoid action. Up-regulation of 11β-HSD1 in adipose tissue and liver is of pathogenic importance in metabolic syndrome. However, the mechanisms controlling 11β-HSD1 transcription are poorly understood. Glucocorticoids themselves potently increase 11β-HSD1 expression in many cells, providing a potential feed-forward system to pathology. We have investigated the molecular mechanisms by which glucocorticoids regulate transcription of 11β-HSD1, exploiting an A549 cell model system in which endogenous 11β-HSD1 is expressed and is induced by dexamethasone. We show that glucocorticoid induction of 11β-HSD1 is indirect and requires new protein synthesis. A glucocorticoid-responsive region maps to between −196 and −88 with respect to the transcription start site. This region contains two binding sites for CCAAT/enhancer-binding protein (C/EBP) that together are essential for the glucocorticoid response and that bind predominantly C/EBPβ, with C/EBPδ present in a minority of the complexes. Both C/EBPβ and C/EBPδ are rapidly induced by glucocorticoids in A549 cells, but small interfering RNA-mediated knockdown shows that only C/EBPβ reduction attenuates the glucocorticoid induction of 11β-HSD1. Chromatin immunoprecipitation studies demonstrated increased binding of C/EBPβ to the 11β-HSD1 promoter in A549 cells after glucocorticoid treatment. A similar mechanism may apply in adipose tissue in vivo where increased C/EBPβ mRNA levels after glucocorticoid treatment were associated with increased 11β-HSD1 expression. C/EBPβ is a key mediator of metabolic and inflammatory signaling. Positive regulation of 11β-HSD1 by C/EBPβ may link amplification of glucocorticoid action with metabolic and inflammatory pathways and may represent an endogenous innate host-defense mechanism.


2012 ◽  
Vol 287 (41) ◽  
pp. 34349-34360 ◽  
Author(s):  
Shaikh M. Rahman ◽  
Rachel C. Janssen ◽  
Mahua Choudhury ◽  
Karalee C. Baquero ◽  
Rebecca M. Aikens ◽  
...  

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