Distal-less homeobox 5 inhibits adipogenic differentiation through the down-regulation of peroxisome proliferator-activated receptor γ expression

2012 ◽  
Vol 228 (1) ◽  
pp. 87-98 ◽  
Author(s):  
Hye-Lim Lee ◽  
Kyung Mi Woo ◽  
Hyun-Mo Ryoo ◽  
Jeong-Hwa Baek
Keyword(s):  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Down Regulation ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Zidovudine Impairs Adipogenic Differentiation through Inhibition of Clonal Expansion

2008 ◽  
Vol 52 (8) ◽  
pp. 2882-2889 ◽  
Author(s):  
Metodi V. Stankov ◽  
Reinhold E. Schmidt ◽  
Georg M. N. Behrens
Keyword(s):  
Adipogenic Differentiation ◽  
Clonal Expansion ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Triglyceride Accumulation ◽  
Thymidine Incorporation Assay ◽  
Human Preadipocytes ◽  
Incorporation Assay ◽  
The Impact

ABSTRACT Lipoatrophy is a prevalent side effect of treatment with thymidine analogues. We wished to confine the time point of the antiadipogenic effect of zidovudine (AZT) during adipogenesis and to evaluate the antiproliferative effect of AZT on adipocyte homeostasis. We investigated the effects of AZT on adipogenesis in 3T3-F442A cells and studied their proliferation, differentiation, viability, and adiponectin expression. Cells were exposed to AZT (1 μM, 3 μM, 6 μM, and 180 μM), stavudine (d4T; 3 μM), or dideoxycytosine (ddC; 0.1 μM) for up to 15 days. Differentiation was assessed by real-time PCR and quantification of triglyceride accumulation. Proliferation and clonal expansion were determined by a [3H]thymidine incorporation assay. When they were induced to differentiate in the presence of AZT at the maximum concentration in plasma (C max) and lower concentrations, 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol and failed to express normal levels of the later adipogenic transcription factors, CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ. AZT exerted an inhibitory effect on the completion of the mitotic clonal expansion, which resulted in incomplete 3T3-F442A differentiation and, finally, a reduction in the level of adiponectin expression. In addition, AZT impaired the constitutive proliferation in murine and primary human subcutaneous preadipocytes. In contrast, incubation with d4T and ddC at the C max did not affect either preadipocyte proliferation or clonal expansion and differentiation. We conclude that the antiproliferative and antiadipogenetic effects of AZT on murine and primary human preadipocytes reveal the impact of the drug on fat tissue regeneration. These effects of the drug are expected to contribute to disturbed adipose tissue homeostasis and to be influenced by differential drug concentration and penetration in individual patients.

scholarly journals Myricetin Increases Hepatic Peroxisome Proliferator-Activated ReceptorαProtein Expression and Decreases Plasma Lipids and Adiposity in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Chia Ju Chang ◽  
Thing-Fong Tzeng ◽  
Shorong-Shii Liou ◽  
Yuan-Shiun Chang ◽  
I-Min Liu
Keyword(s):  
Plasma Lipids ◽  
Regulatory Element ◽  
Plasma Lipid ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Down Regulation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Once Daily ◽  
Sterol Regulatory Element ◽  
Lowered Body

The aim of this study was to investigate the antiobesity and antihyperlipidaemic effects of myricetin. Myricetin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3T3-L1 adipocytes. The high-fat diet (HFD)-fed rats were dosed orally with myricetin or fenofibrate, once daily for eight weeks. Myricetin (300 mg kg−1per day) displayed similar characteristics to fenofibrate (100 mg kg−1per day) in reducing lowered body weight (BW) gain, visceral fat-pad weights and plasma lipid levels of HFD-fed rats. Myricetin also reduced the hepatic triglyceride and cholesterol contents, as well as lowered hepatic lipid droplets accumulation and epididymal adipocyte size in HFD-fed rats. Myricetin and fenofibrate reversed the HFD-induced down-regulation of the hepatic peroxisome proliferator activated receptor (PPAR)α. HFD-induced decreases of the hepatic protein level of acyl-CoA oxidase and cytochrome P450 isoform 4A1 were up-regulated by myricetin and fenofibrate. The elevated expressions of hepatic sterol regulatory element binding proteins (SREBPs) of HFD-fed rats were lowered by myricetin and fenofibrate. These results suggest that myricetin suppressed BW gain and body fat accumulation by increasing the fatty acid oxidation, which was likely mediated via up-regulation of PPARαand down-regulation of SREBP expressions in the liver of HFD-fed rats.

scholarly journals LKB1 signalling attenuates early events of adipogenesis and responds to adipogenic cues

2014 ◽  
Vol 53 (1) ◽  
pp. 117-130 ◽  
Author(s):  
Amélie Gormand ◽  
Christine Berggreen ◽  
Lahouari Amar ◽  
Emma Henriksson ◽  
Ingrid Lund ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Histone Deacetylases ◽  
Fatty Acid Synthase ◽  
Nuclear Translocation ◽  
Adipogenic Differentiation ◽  
Camp Response Element Binding ◽  
Dominant Negative ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

cAMP-response element-binding protein (CREB) is required for the induction of adipogenic transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs). Interestingly, it is known from studies in other tissues that LKB1 and its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases (SIKs) negatively regulate gene expression by phosphorylating the CREB co-activator CRTC2 and class IIa histone deacetylases (HDACs), which results in their exclusion from the nucleus where they co-activate or inhibit their targets. In this study, we show that AMPK/SIK signalling is acutely attenuated during adipogenic differentiation of 3T3-L1 preadipocytes, which coincides with the dephosphorylation and nuclear translocation of CRTC2 and HDAC4. When subjected to differentiation, 3T3-L1 preadipocytes in which the expression of LKB1 was stably reduced using shRNA (Lkb1-shRNA), as well as Lkb1-knockout mouse embryonic fibroblasts (Lkb1−/− MEFs), differentiated more readily into adipocyte-like cells and accumulated more triglycerides compared with scrambled-shRNA-expressing 3T3-L1 cells or Wt MEFs. In addition, the phosphorylation of CRTC2 and HDAC4 was reduced, and the mRNA expression of adipogenic transcription factors Cebpa, peroxisome proliferator-activated receptor γ (Pparg) and adipocyte-specific proteins such as hormone-sensitive lipase (HSL), fatty acid synthase (FAS), aP2, GLUT4 and adiponectin was increased in the absence of LKB1. The mRNA and protein expression of Ddit3/CHOP10, a dominant-negative member of the C/EBP family, was reduced in Lkb1-shRNA-expressing cells, providing a potential mechanism for the up-regulation of Pparg and Cebpa expression. These results support the hypothesis that LKB1 signalling keeps preadipocytes in their non-differentiated form.

scholarly journals Bisphenol A enhances adipogenic differentiation of human adipose stromal/stem cells

2014 ◽  
Vol 53 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Jason F Ohlstein ◽  
Amy L Strong ◽  
John A McLachlan ◽  
Jeffrey M Gimble ◽  
Matthew E Burow ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bisphenol A ◽  
Leucine Zipper ◽  
Adipogenic Differentiation ◽  
Density Measurement ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein ◽  
Pm 10 ◽  
Stromal Stem Cells

Exposure of humans to the endocrine disrupter bisphenol A (BPA) has been associated with increased weight and obesity. However, the mechanism(s) by which BPA increases adipose tissue in humans remains to be determined. The goal of this study was to determine the effects of BPA on adipogenesis of cultured human adipose stromal/stem cells (ASCs), precursors to mature adipocytes. ASCs from three donors were cultured for either 14 or 21 days in adipogenic differentiation media containing increasing concentrations of BPA (100 pM–10 μM). The extent of adipogenic differentiation in the ASCs was assessed by staining with Oil Red O to visualize adipogenic differentiation and then quantified by extraction and optical density measurement of the retained dye. BPA significantly enhanced adipogenesis at a concentration of 1 μM after 21 days of culture. Additionally, we found that BPA increased transcription of the estrogen receptor (ER (ESR1)) and that treatment with the ER antagonist ICI 182 780, blocked the effects of BPA, indicating that BPA may act via an ER-mediated pathway. The results of molecular analyses indicated that the expression of the adipogenesis-associated genes dual leucine zipper-bearing kinase (DLK (MAP3K12)), IGF1, CCAAT/enhancer-binding protein alpha (C/EBPα (CEBPA)), peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), and lipoprotein lipase (LPL) was temporally accelerated and increased by BPA. In summary, these results indicate that BPA significantly enhances adipogenesis in ASCs through an ER-mediated pathway at physiologically relevant concentrations.

Evaluation of anti-adipogenic active homoisoflavonoids from Portulaca oleracea

2019 ◽  
Vol 74 (9-10) ◽  
pp. 265-273 ◽  
Author(s):  
Jung Im Lee ◽  
Jung Hwan Oh ◽  
Chang-Suk Kong ◽  
Youngwan Seo
Keyword(s):  
Fatty Acid ◽  
Crude Extract ◽  
Lipid Accumulation ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Portulaca Oleracea ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding

Abstract This study was performed to isolate antiobesity components from the crude extract of Portulaca oleracea. The crude extract was partitioned into n-hexane, 85% aqueous methanol, n-butanol, and water fractions. Their effects on adipogenic differentiation were evaluated in 3T3-L1 cells. Among the solvent fractions from P. olearacea, the 85% aq. MeOH effectively reduced the levels of lipid accumulation. Further purification of 85% aq. MeOH led to the isolation of the known homoisoflavonoids 1–4, as the active substances. The administration of homoisoflavonoids to adipocyte cells decreased the lipid accumulation and glucose consumption and increased the release of glycerol into culture medium. In particular, homoisoflavonoid 3 effectively down-regulated the adipogenic transcription genes such as peroxisome proliferator activated receptor-γ (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPα), and adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid transport protein 1 (FATP1), and acyl-CoA synthase 1 (ACS1).

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