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 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.

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 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 OR14-05 Hepatocyte Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Offsets the Anti-Steatogenic Effects of Thiazolidinediones in Obese Male Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jose T Muratalla ◽  
Samuel M Lee ◽  
Pablo Remon-Ruiz ◽  
Gregory H Norris ◽  
Jose Cordoba-Chacon
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Liver Weight ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mild Phenotype ◽  
Insulin Resistant ◽  
Brown Adipose ◽  
Pparg Expression

Abstract Pparg is a nuclear receptor that regulates glucose and lipid metabolism. Thiazolidinediones (TZD) are PPARG agonists that may reduce hepatic steatosis through their effects in adipose tissue. However, some studies suggest that expression and activation of hepatocyte Pparg promotes steatosis. In this study, we have assessed the relevance of hepatocyte Pparg, and its TZD-mediated activation in the development and/or reduction of steatosis, with adult-onset hepatocyte-specific Pparg knockout (PpargΔHep) mice. We reported that a single iv injection of AAV8-TBG-Cre in Pparg-floxed mice, knocked out hepatocyte Pparg expression (PpargΔHep mice), and that prevented diet-induced steatosis. In this study, a group of 5 wk-old Pparg-floxed mice were fed a low fat (LF) or a high fat (HF) diet for 7 weeks before generating control and PpargΔHep mice. Then, half of the HF-fed mice in each group were switched to a HF diet supplemented with the TZD Rosiglitazone maleate, for 5 weeks. HF diet induced mild obesity (36.8 +/- 1.4 g of body weight [BW]), while TZD slightly increased BW (41.3 +/- 1.3 g) and insulin sensitivity. Liver weight was not altered in HF-fed mice with or without TZD, and we did not observe any effect induced by PpargΔHep. Due to the mild phenotype observed in this cohort, we generated a 2nd cohort adjusting for age and length of diet. Briefly, 10 wk-old Pparg-floxed mice were fed a LF or HF diet for 16 weeks before generating control and PpargΔHep mice. Then, half of the HF-fed mice in each group were switched to a HF diet supplemented with Rosiglitazone maleate for 7 weeks. In this group of mice, HF diet induced obesity (50.1 +/- 1.05 g BW), and increased liver weight independent of hepatic Pparg expression. TZD treatment exacerbated obesity (62.4 +/- 1.2g BW) and adiposity, but increased insulin sensitivity as compared to mice fed a HF diet without TZD. Interestingly, PpargΔHep mice fed a HF diet with TZD showed enlarged subcutaneous white and brown adipose tissue weight, and a dramatic reduction in liver weight and steatosis as compared to obese control mice treated with TZD. The expression of hepatic Cd36, Cidea, Cidec, and Fabp4 was increased by TZD in a Pparg-dependent manner in HF-fed mice. Altogether, this data suggest that hepatocyte Pparg expression may offset the antisteatogenic actions of TZD in mice with severe obesity. In obese and insulin resistant individuals, TZD-mediated activation of hepatocyte Pparg may exacerbate steatosis.

Depot-Specific Analysis of Human Adipose Cells and Their Responses to Bisphenol S

Endocrinology ◽  
2020 ◽  
Vol 161 (6) ◽  
Author(s):  
Vian Peshdary ◽  
George Styles ◽  
Rémi Gagné ◽  
Carole L Yauk ◽  
Alexander Sorisky ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Endocrine Disrupting Chemicals ◽  
Environmental Pollutants ◽  
Visceral Obesity ◽  
Gene Expression Profiles ◽  
Peroxisome Proliferator ◽  
Bisphenol S ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adverse Health Outcomes ◽  
Obesity And Diabetes

Abstract Exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse health outcomes including obesity and diabetes. Obesity, and more specifically visceral obesity, is correlated with metabolic disease. The adipose tissue is an endocrine organ and a potential target for many environmental pollutants including bisphenols. The subcutaneous (Sc) and the omental (Om, visceral) depots are composed of mature adipocytes and residing progenitors, which may be different between the depots and may be EDCs targets. Bisphenol A (BPA) is a suspected metabolic disruptor, and is being replaced with structurally similar compounds such as bisphenol S (BPS). Like BPA, BPS induces adipogenesis in murine and primary human Sc preadipocytes. However, the effect of BPS on Om preadipocytes is not known. In this study, we show that human primary progenitors from Om depots have a distinct transcriptomic signature as compared to progenitors derived from donor-matched Sc depots. Furthermore, we show that BPS increases adipogenesis both of Om and Sc preadipocytes and can mimic the action of glucocorticoids or peroxisome proliferator-activated receptor γ (PPARγ) agonists. We also show that BPS treatment, at 0.1 µM and 25 µM, modifies the adipokine profiles both of Om- and Sc-derived adipocytes in a depot-specific manner. Taken together our data show distinct gene expression profiles in the Om vs Sc progenitors and similar responses to the BPA analogue, BPS.

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