scholarly journals Transcription Coactivator PBP, the Peroxisome Proliferator-activated Receptor (PPAR)-binding Protein, Is Required for PPARα-regulated Gene Expression in Liver

2004 ◽  
Vol 279 (23) ◽  
pp. 24427-24434 ◽  
Author(s):  
Yuzhi Jia ◽  
Chao Qi ◽  
Papreddy Kashireddi ◽  
Sailesh Surapureddi ◽  
Yi-Jun Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Regulated Gene Expression ◽  
Transcription Coactivator

scholarly journals Lipid Metabolism Gene Expression And Cellularity of Intramuscular Adipocytes Within The Longissimus Muscle of Angus- And Wagyu-Sired Cattle When Raised To A Similar Age or Body Weight

2021 ◽  
Author(s):  
Jerad Jaborek ◽  
Francis Fluharty ◽  
Kichoon Lee ◽  
Henry Zerby ◽  
Alejandro Relling
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Longissimus Muscle ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipid Metabolism Gene ◽  
Metabolism Gene

Abstract Background: This study investigates intramuscular (IM) adipocyte development and growth in the Longissimus muscle (LM) between Wagyu- and Angus-sired steers compared at a similar age and days on feed (DOF) endpoint or similar body weight (BW) endpoint by measuring IM adipocyte cell area and lipid metabolism gene expression. Methods: Angus-sired steers (AN, n=6) were compared with steers from two different Wagyu sires, selected for either growth or marbling, to be compared at a similar DOF (WA-GD, n=5 and WA-MD, n=5) in experiment 1 or BW (WA-GB, n=4 and WA-MB, n=5) in experiment 2, respectively. Results: In experiment 1, WA-MD steers had a greater percentage of IM fat in the LM compared with AN and WA-GD steers. In experiment 2, WA-MB steers had a greater percentage of IM fat in the LM compared with AN and WA-GB steers. The distribution of IM adipocyte area was unimodal at all biopsy collections, with IM adipocyte area becoming progressively larger as cattle age and BW increased (P≤0.01). Peroxisome proliferator activated receptor delta (PPARd) was upregulated earlier for WA-MD and WA-MB cattle compared with other steers at a similar age and BW (P≤0.02; treatment×biopsy interaction). An earlier upregulation of PPARd is believed to have then upregulated peroxisome proliferator activated receptor gamma (PPARg) at a lesser BW for WA-MB steers (P=0.09; treatment×biopsy interaction), while WA-MD steers had a greater (P≤0.04) overall mean PPARg expression compared with other steers. Glycerol-3-phosphate acyltransferase, lipin 1, and hormone sensitive lipase demonstrated expression patterns similar to PPARg and PPARd or CCAAT enhancer binding protein beta, which emphasizes their importance in marbling development and growth. Additionally, WA-MD and WA-MB steers often had a greater early expression of fatty acid transporters (fatty acid transport protein 1; P<0.02; treatment×biopsy interaction) and binding proteins (fatty acid binding protein 4) compared with other steers. With many lipolytic genes upregulated at harvest, acetyl-CoA carboxylase beta may be inhibiting fatty acid oxidation in the LM to allow greater IM fat accumulation.Conclusions: Cattle with a greater marbling propensity appear to upregulate adipogenesis at a lesser maturity through PPARd, PPARg, and possibly adipogenic regulating compounds in lysophosphatidic acid and diacylglycerol.

scholarly journals Transcription Suppression of Peroxisome Proliferator-Activated Receptor γ2 Gene Expression by Tumor Necrosis Factor α via an Inhibition of CCAAT/ Enhancer-binding Protein δ during the Early Stage of Adipocyte Differentiation

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4948-4956 ◽  
Author(s):  
Masataka Kudo ◽  
Akira Sugawara ◽  
Akira Uruno ◽  
Kazuhisa Takeuchi ◽  
Sadayoshi Ito
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Gene Transcription ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Enhancer Binding Protein

Abstract TNFα is known to inhibit adipocyte differentiation and induce insulin resistance. Moreover, TNFα is known to down-regulate peroxisome proliferator-activated receptor (PPAR)γ2, an adipocyte-specific nuclear receptor of insulin-sensitizer thiazolidinediones. To clarify molecular mechanisms of TNFα- mediated PPARγ2 down-regulation, we here examined the effect of TNFα on transcription regulation of PPARγ2 gene expression during the early stage of adipocyte differentiation. 3T3-L1 preadipocytes (2 d after 100% confluent) were incubated in a differentiation mixture (dexamethasone, insulin, 3-isobutyl-1-methlxanthine), with or without 50 ng/ml TNFα, for 24 h. TNFα significantly decreased PPARγ2 expression both at mRNA and protein levels (to ∼40%), as well as aP2 mRNA expression. The mouse PPARγ2 gene promoter region (2.2-kb) was isolated and was used for luciferase reporter assays by transient transfection. TNFα significantly suppressed PPARγ2 gene transcription (to ∼50%), and deletion analyses demonstrated that the suppression was mediated via CCAAT/enhancer-binding protein (C/EBP) binding elements at the −320/−340 region of the promoter. Moreover, TNFα significantly decreased expression of C/EBPδ mRNA and protein levels (to ∼40%). EMSA, using 3T3-L1 cells nuclear extracts with the −320/−340 region as a probe, demonstrated the binding of C/EBPδ to the element, which was significantly decreased by TNFα treatment. Overexpression of CEBP/δ prevented the TNFα-mediated suppression of PPARγ2 transactivation. Taken together, TNFα suppresses PPARγ2 gene transcription by the inhibition of C/EBPδ expression and its DNA binding during the early stage of adipocyte differentiation, which may contribute to the inhibition of adipocyte differentiation, as well as the induction of insulin resistance.

scholarly journals Suppression of Adiponectin Gene Expression by Histone Deacetylase Inhibitor Valproic Acid

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 865-874 ◽  
Author(s):  
Liping Qiao ◽  
Jerome Schaack ◽  
Jianhua Shao
Keyword(s):  
Gene Expression ◽  
Valproic Acid ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Adiponectin Gene ◽  
Peroxisome Proliferator Activated Receptor ◽  
Deacetylase Inhibitor

Valproic acid (VPA) has been used for the treatment of epilepsy and bipolar disorders for more than 30 yr. Obesity and insulin resistance are common side effects of VPA treatment. Adiponectin is an adipocyte-derived protein that plays an important role in controlling insulin sensitivity and glucose homeostasis. In this report, we examined the effects of VPA on adiponectin gene expression in C57BL/6J mice and in differentiated 3T3-L1 adipocytes. VPA treatment significantly decreased adiponectin protein and mRNA levels in both mice and 3T3-L1 adipocytes. The adipocyte study showed that VPA inhibited adiponectin gene expression in a dose- and time-dependent manner. Repression of adiponectin expression by VPA occurred at the transcription level and correlated with inhibition of histone deacetylase activity. Therapeutic concentrations of VPA increased overall histone acetylation and increased adiponectin promoter-driven luciferase expression in fibroblasts, but decreased adiponectin promoter activity in differentiated 3T3-L1 adipocytes. VPA treatment decreased adipogenic transcription factor CCAAT/enhancer binding protein-α (C/EBPα) levels and binding of C/EBPα to the adiponectin promoter without altering the levels of peroxisome proliferator-activated receptor-γ and steroid regulatory element binding protein-1. Furthermore, VPA did not suppress adiponectin gene expression in C/EBPα gene-deficient adipocytes that stably expressed exogenous peroxisome proliferator-activated receptor-γ2. Together, these results demonstrate that histone deacetylase inhibitor VPA suppresses adiponectin gene expression in mature adipocytes. The study also provides evidence that diminished C/EBPα protein level and decreased binding at the adiponectin promoter mediate the inhibitory effects of VPA on adiponectin gene transcription.

scholarly journals C/EBP transcription factors regulate SREBP1c gene expression during adipogenesis

2009 ◽  
Vol 425 (1) ◽  
pp. 215-224 ◽  
Author(s):  
Victoria A. Payne ◽  
Wo-Shing Au ◽  
Christopher E. Lowe ◽  
Shaikh M. Rahman ◽  
Jacob E. Friedman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Binding Protein ◽  
Regulatory Element ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Small Interfering Rnas ◽  
Inhibitory Protein ◽  
Intact Cells ◽  
Peroxisome Proliferator Activated Receptor

The transcription factor SREBP1c (sterol-regulatory-element-binding protein 1c) is highly expressed in adipose tissue and plays a central role in several aspects of adipocyte development including the induction of PPARγ (peroxisome-proliferator-activated receptor γ), the generation of an endogenous PPARγ ligand and the expression of several genes critical for lipid biosynthesis. Despite its significance, the regulation of SREBP1c expression during adipogenesis is not well characterized. We have noted that in several models of adipogenesis, SREBP1c expression closely mimics that of known C/EBPβ (CCAAT/enhancer-binding protein β) targets. Inhibition of C/EBP activity during adipogenesis by expressing either the dominant-negative C/EBPβ LIP (liver-enriched inhibitory protein) isoform, the co-repressor ETO (eight-twenty one/MTG8) or using siRNAs (small interfering RNAs) targeting either C/EBPβ or C/EBPδ significantly impaired early SREBP1c induction. Furthermore, ChIP (chromatin immunoprecipitation) assays identified specific sequences in the SREBP1c promoter to which C/EBPβ and C/EBPδ bind in intact cells, demonstrating that these factors may directly regulate SREBP1c expression. Using cells in which C/EBPα expression is inhibited using shRNA (short hairpin RNA) and ChIP assays we show that C/EBPα replaces C/EBPβ and C/EBPδ as a regulator of SREBP1c expression in maturing adipocytes. These results provide novel insight into the induction of SREBP1c expression during adipogenesis. Moreover, the findings of the present study identify an important additional mechanism via which the C/EBP transcription factors may control a network of gene expression regulating adipogenesis, lipogenesis and insulin sensitivity.

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