scholarly journals Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate

2019 ◽  
Vol 20 (22) ◽  
pp. 5682 ◽  
Author(s):  
Yusuke Sasaki ◽  
Sana Raza-Iqbal ◽  
Toshiya Tanaka ◽  
Kentaro Murakami ◽  
Motonobu Anai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Vascular Endothelial Cells ◽  
Expression Profiles ◽  
Microvascular Complications ◽  
Density Lipoprotein ◽  
Gene Expression Profiles ◽  
Atherogenic Dyslipidemia ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Pemafibrate is the first clinically-available selective peroxisome proliferator-activated receptor α modulator (SPPARMα) that has been shown to effectively improve hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. Global gene expression analysis reveals that the activation of PPARα by pemafibrate induces fatty acid (FA) uptake, binding, and mitochondrial or peroxisomal oxidation as well as ketogenesis in mouse liver. Pemafibrate most profoundly induces HMGCS2 and PDK4, which regulate the rate-limiting step of ketogenesis and glucose oxidation, respectively, compared to other fatty acid metabolic genes in human hepatocytes. This suggests that PPARα plays a crucial role in nutrient flux in the human liver. Additionally, pemafibrate induces clinically favorable genes, such as ABCA1, FGF21, and VLDLR. Furthermore, pemafibrate shows anti-inflammatory effects in vascular endothelial cells. Pemafibrate is predicted to exhibit beneficial effects in patients with atherogenic dyslipidemia and diabetic microvascular complications.

Functional genomic characterization of delipidation elicited by trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice

2005 ◽  
Vol 21 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Ralph L. House ◽  
Joseph P. Cassady ◽  
Eugene J. Eisen ◽  
Thomas E. Eling ◽  
Jennifer B. Collins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Linoleic Acid ◽  
Glucose Transporter ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Liver Weight ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adult Mice ◽  
Brown Adipose

Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice ( n = 185) were allotted to a 2 × 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or 1% t10c12-CLA. Body weight (BW) by day 14 was 12% lower in CLA- compared with LA-fed mice ( P < 0.0001). By day 14, t10c12-CLA reduced weights of epididymal, mesenteric, and brown adipose tissues, as a percentage of BW, in both lines by 30, 27, and 58%, respectively, and increased liver weight/BW by 34% ( P < 0.0001). Total RNA was isolated and pooled (4 pools per tissue per day) from epididymal adipose ( days 5 and 14) of the obese mice to analyze gene expression profiles using Agilent mouse oligo microarray slides representing >20,000 genes. Numbers of genes differentially expressed by greater than or equal to twofold in epididymal adipose ( days 5 and 14) were 29 and 125, respectively. It was concluded that, in adipose tissue, CLA increased expression of uncoupling proteins (1 and 2), carnitine palmitoyltransferase system, tumor necrosis factor-α ( P < 0.05), and caspase-3 but decreased expression of peroxisome proliferator-activated receptor-γ, glucose transporter-4, perilipin, caveolin-1, adiponectin, resistin, and Bcl-2 ( P < 0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms of adipose delipidation.

scholarly journals Comparison of gene expression profiles between human and mouse monocyte subsets

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. e10-e19 ◽  
Author(s):  
Molly A. Ingersoll ◽  
Rainer Spanbroek ◽  
Claudio Lottaz ◽  
Emmanuel L. Gautier ◽  
Marion Frankenberger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Surface Protein ◽  
Human Monocyte ◽  
Peroxisome Proliferator ◽  
Cell Surface Protein ◽  
Monocyte Subsets ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human And Mouse

Abstract Blood of both humans and mice contains 2 main monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 270 genes in humans and 550 genes in mice were differentially expressed between subsets by 2-fold or more. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous of these differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the 2 species' subsets, including CD36, CD9, and TREM-1. Other differences included a prominent peroxisome proliferator-activated receptor γ (PPARγ) signature in mouse monocytes, which is absent in humans, and strikingly opposed patterns of receptors involved in uptake of apoptotic cells and other phagocytic cargo between human and mouse monocyte subsets. Thus, whereas human and mouse monocyte subsets are far more broadly conserved than currently recognized, important differences between the species deserve consideration when models of human disease are studied in mice.

scholarly journals Caffeic and Chlorogenic Acids Synergistically Activate Browning Program in Human Adipocytes: Implications of AMPK- and PPAR-Mediated Pathways

2020 ◽  
Vol 21 (24) ◽  
pp. 9740
Author(s):  
Liliya V. Vasileva ◽  
Martina S. Savova ◽  
Kristiana M. Amirova ◽  
Zhivka Balcheva-Sivenova ◽  
Claudio Ferrante ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metabolic Effects ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Human Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ampk Signaling

Caffeic acid (CA) and chlorogenic acid (CGA) are phenolic compounds claimed to be responsible for the metabolic effects of coffee and tea consumption. Along with their structural similarities, they share common mechanisms such as activation of the AMP-activated protein kinase (AMPK) signaling. The present study aimed to investigate the anti-obesity potential of CA and CGA as co-treatment in human adipocytes. The molecular interactions of CA and CGA with key adipogenic transcription factors were simulated through an in silico molecular docking approach. The expression levels of white and brown adipocyte markers, as well as genes related to lipid metabolism, were analyzed by real-time quantitative PCR and Western blot analyses. Mechanistically, the CA/CGA combination induced lipolysis, upregulated AMPK and browning gene expression and downregulated peroxisome proliferator-activated receptor γ (PPARγ) at both transcriptional and protein levels. The gene expression profiles of the CA/CGA-co-treated adipocytes strongly resembled brown-like signatures. Major pathways identified included the AMPK- and PPAR-related signaling pathways. Collectively, these findings indicated that CA/CGA co-stimulation exerted a browning-inducing potential superior to that of either compound used alone which merits implementation in obesity management. Further, the obtained data provide additional insights on how CA and CGA modify adipocyte function, differentiation and lipid metabolism.

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 Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1498 ◽  
Author(s):  
Elisa Belloni ◽  
Anna Di Matteo ◽  
Davide Pradella ◽  
Margherita Vacca ◽  
Christopher D. R. Wyatt ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Protein Isoforms ◽  
Peroxisome Proliferator ◽  
Bioinformatics Analyses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Significant Enrichment ◽  
Steady State Levels

Alternative splicing (AS) plays an important role in expanding the complexity of the human genome through the production of specialized proteins regulating organ development and physiological functions, as well as contributing to several pathological conditions. How AS programs impact on the signaling pathways controlling endothelial cell (EC) functions and vascular development is largely unknown. Here we identified, through RNA-seq, changes in mRNA steady-state levels in ECs caused by the neuro-oncological ventral antigen 2 (Nova2), a key AS regulator of the vascular morphogenesis. Bioinformatics analyses identified significant enrichment for genes regulated by peroxisome proliferator-activated receptor-gamma (Ppar-γ) and E2F1 transcription factors. We also showed that Nova2 in ECs controlled the AS profiles of Ppar-γ and E2F dimerization partner 2 (Tfdp2), thus generating different protein isoforms with distinct function (Ppar-γ) or subcellular localization (Tfdp2). Collectively, our results supported a mechanism whereby Nova2 integrated splicing decisions in order to regulate Ppar-γ and E2F1 activities. Our data added a layer to the sequential series of events controlled by Nova2 in ECs to orchestrate vascular biology.

scholarly journals Beta-sitosterol upregulated paraoxonase-1 via peroxisome proliferator-activated receptor-γ in irradiated rats

2017 ◽  
Vol 95 (6) ◽  
pp. 661-666 ◽  
Author(s):  
Enas Mahmoud Moustafa ◽  
Noura Magdy Thabet
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Enzyme Activities ◽  
Liver Tissue ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Oxidative Stress Marker ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

This study was designed to evaluate the effect of beta-sitosterol (BS) on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression role in the activity of paraoxonase (PON-1) enzyme in oxidative stress status of irradiated rats. Animals were exposed to whole body γ-radiation single dose 6 Gy and received BS dose (40 mg·(kg body mass)−1·day−1, orally). In liver tissue, gene expression of PPAR-γ ligand was determined. Oxidative stress marker (malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), PON-1, and arylesterase (ARE)) were assayed in serum and liver tissue. Also, serum lipid profile (cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) was measured. In irradiated animals that received BS, expression of PPAR-γ ligand increase significantly associated with increase in PON-1 and ARE enzyme activities. Also, the activities of SOD, CAT enzymes, and HDL-c levels display elevation. By contrast, significant decrease in MDA content, cholesterol, TG, and LDL-c levels were revealed after BS administration. Our findings in this study provide the evidence that BS has radio-protective effect via regulating the gene expression of PPAR-γ, causing an increase in PON-1 and ARE enzyme activities. This action of BS is due to its free radical scavenging properties, antioxidant effect, lowering of cholesterol, and PPAR-γ agonist properties.

Sign in / Sign up

Export Citation Format

Share Document