Gene expression in adipose, liver and skeletal muscle of mice fed a diet with c9, t11 conjugated linoleic acid enriched beef
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE23337 | GEO | 2010/10/19
SECONDARY ACCESSION(S): PRJNA131221
REPOSITORIES: GEO
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Project description:Conjugated Linoleic Acid (CLA) is a collective term for the positional and geometric isomers of linoleic acid. In recent years CLA has been reported to have anti-carcinogenic, anti-obesity, anti-inflammatory and anti-artherogenic effects. The aim of this study was to determine the effects of a natural high-CLA enriched beef source on three primary insulin responsive tissues: adipose, liver and skeletal muscle. ob/ob mice were assigned to one of two diets: a control beef diet, low in c9, t11-CLA (control diet) or a c9, t11-CLA enriched beef diet. After a 28 day feeding trial, RNA was extracted from adipose, liver and skeletal muscle tissue and hybridized to Affymetrix microarrays.
2010-10-19 | E-GEOD-23337 | biostudies-arrayexpress
Project description:Overexpression of fatty acid synthase (FAS) has been reported in both malignant and premalignant breast lesions, and has been associated with poor outcome. FAS has gained interest as a metabolic target for the treatment of breast cancer based on evidence that blockade with the antifungal antibiotic, cerulenin or synthetic inhibitor C75 inhibits proliferation of breast cancer cells and delays tumor development. Conjugated linoleic acid (CLA), a class of fatty acids found in beef and dairy products, has been shown to inhibit FAS in bovine mammary adipose. Based on previously well-documented anti-tumor activity of CLA, we hypothesized that one mechanism of CLA’s anti-tumorigenic activity may be metabolic blockade of FAS. We fed virgin PyV-MT transgenic mice a diet supplemented with either 1% CLA, as mixed isomers, or control chow for four weeks. Tissue histology was determined by H&E staining. cDNA microarray and real-time quantitative PCR were performed to determine relative expression of lipogenic genes. Western blots were used to examine relative protein expression of FAS. Differences in protein densitometry were analyzed using Students 2-sided T-test. Probability was determined using the binomial sign test. Level of significance for all tests was 0.05. H&E staining revealed a shift towards advanced mammary lesions in the CLA-fed mice compared to control animals (24/26 vs. 11/26) (p for trend < 0.001). Microarray analysis revealed a >2-fold decrease in FAS in the CLA-fed group compared to controls, and was confirmed by quantitative RT-PCR (p < 0.001) and Western blot. The decrease in FAS mRNA expression was unexpectedly associated with more advanced disease (p for trend < 0.01). Conclusions: Dietary CLA suppressed fatty acid synthase in the mammary glands of the PyV-MT mouse while promoting mammary tumor progression. Keywords: dietary intervention to compare mammary tumorigenesis between groups
2008-01-17 | GSE10193 | GEO
Project description:Objective: To quantify changes in adipogenic gene expression in the presence of ritonavir (RTV) or tenofovir (TDF), and determine whether conjugated linoleic acid (CLA) isomers (cis9,trans11 or trans10,cis12) can mitigate detrimental effects of antiretoviral drugs. Methods: Affymetrix Mouse Genome 430 2.0 microarray was used to investigate gene expression in 3T3-L1 adipocytes treated with (1) RTV, TDF or ethanol control, or (2) ritonavir +c9,t11-CLA, ritonavir+t10,c12-CLA or ritonavir+DMSO control. RT-PCR validation of Pparg, Adipoq and Retn was carried out. ELISA and DNA binding ELISA were used to investigate secreted proteins and Pparg binding to its gene response element. Oil Red O staining was used to investigate triglyceride accumulation. Results: No effect was observed for TDF. Expression of 389 genes was altered more than 5-fold in the presence of RTV. Down-regulated genes included Pparg, Adipoq, Retn, Cfd and Cidec. Pparg and Adipoq down-regulation were confirmed by RT-PCR. PPAR-γ binding to its gene response element, adiponectin protein secretion and triglyceride accumulation were decreased by RTV. t10,c12-CLA in the presence of RTV decreased the expression of Ppargand Adipoq in microarray and RT-PCR. c9,t11-CLA increased PPAR-γ binding to its gene response element. Both isomers increased triglyceride storage in the presence of RTV. Conclusion: Ritonavir altered genes involved in adipocyte differentiation, lipid accumulation and glucose metabolism. Down-regulation of Pparg may be mediated by changes in Cepba and regulatory genes Pparg1c and Nr1h3.
2016-07-07 | GSE70854 | GEO
Project description:Objective: To quantify changes in adipogenic gene expression in the presence of ritonavir (RTV) or tenofovir (TDF), and determine whether conjugated linoleic acid (CLA) isomers (cis9,trans11 or trans10,cis12) can mitigate detrimental effects of antiretoviral drugs. Methods: Affymetrix Mouse Genome 430 2.0 microarray was used to investigate gene expression in 3T3-L1 adipocytes treated with (1) RTV, TDF or ethanol control, or (2) ritonavir +c9,t11-CLA, ritonavir+t10,c12-CLA or ritonavir+DMSO control. RT-PCR validation of Pparg, Adipoq and Retn was carried out. ELISA and DNA binding ELISA were used to investigate secreted proteins and Pparg binding to its gene response element. Oil Red O staining was used to investigate triglyceride accumulation. Results: No effect was observed for TDF. Expression of 389 genes was altered more than 5-fold in the presence of RTV. Down-regulated genes included Pparg, Adipoq, Retn, Cfd and Cidec. Pparg and Adipoq down-regulation were confirmed by RT-PCR. PPAR-γ binding to its gene response element, adiponectin protein secretion and triglyceride accumulation were decreased by RTV. t10,c12-CLA in the presence of RTV decreased the expression of Ppargand Adipoq in microarray and RT-PCR. c9,t11-CLA increased PPAR-γ binding to its gene response element. Both isomers increased triglyceride storage in the presence of RTV. Conclusion: Ritonavir altered genes involved in adipocyte differentiation, lipid accumulation and glucose metabolism. Down-regulation of Pparg may be mediated by changes in Cepba and regulatory genes Pparg1c and Nr1h3. 3T3-L1 adipocytes were treated with ritonavir (20μM; n=4), tenofovir (1μM; n=4) or vehicle control (ethanol 0.1%; n=4) for 5 days and in a second experiment with ritonavir (20 µM) +c9,t11-CLA (100μM; n=4), ritonavir (20 µM) +t10,c12-CLA (100μM; n=4) or ritonavir+fatty acid vehicle control (DMSO 0.1%; n=4) for 5 days.
2016-07-07 | E-GEOD-70854 | biostudies-arrayexpress
Project description:The effect of CLA on gene expression in Caco-2 cells Experiment Overall Design: Caco-2 cells were treated with linoleic acid (LA; the parent and control fatty acid) trans-10, cis-12 CLA or cis-9, trans-11 CLA for 12 d.
2008-06-14 | E-GEOD-6518 | biostudies-arrayexpress
Project description:Cis-9, trans-11-conjugated linoleic acid (c9, t11-CLA), a functional fatty acid, is one of the research hotspots in the fields of functional dairy products development because of its multiple beneficial effects in humans and animals. In milk, most c9, t11-CLA is de novo synthesized from trans-11-octadecenoic acid (TVA) and it is confirmed that genes such as stearoyl-coA desaturase 1 (SCD1) play a key role in the synthesis. However, few studies have been reported to deeply elucidate the SCD1-dependent molecular mechanism of cis9, trans11-CLA synthesis and its relationship with the pathways of energy metabolism and lipid metabolism. Therefore, in the present study, MAC-T cells were divided into three groups: CAY group (SCD1-inhibited MAC-T cell model with the addition of CAY, TVA), TVA group (only TVA), and Control group (without CAY, TVA). The relative mRNA expression of SCD1 was measured using real-time PCR, while TVA accumulation and c9, t11 -CLA synthesis were analyzed using gas chromatography (GC). The SCD1-related proteins were firstly screened in MAC-T cells by Tandem Mass Tag (TMT)-based quantitative proteomics analysis, then their functions were annotated by bioinformatic analysis, and finally their relationships with SCD1 were evaluated by parallel reaction monitoring (PRM) analysis and small RNA interference. The results showed that the deficiency of SCD1 led by CAY10566 blocked the synthesis of c9, t11-CLA in MAC-T cells. Sixty-one SCD1-associated proteins were screened and found to be mainly involved in the pathways of energy metabolism and lipid metabolism, such as glycolytic pathway, pentose phosphate pathway, fatty acid elongation pathway, and unsaturated fatty acid biosynthesis. Among these genes, 17 proteins were validated under the PRM analysis. PGAM1 (phosphoglycerate mutase 1), TPI1 (triosephosphate isomerase 1), LDHB (lactate dehydrogenase B), and ALDOA (aldolase, fructose-bisphosphate A) were verified to have a negative relationships with SCD1. This study furthered our understanding of the molecular mechanisms of c9, t11-CLA synthesis in the mammary glands of dairy cows.
2022-08-12 | PXD028620 | Pride
Project description: Not available
| S-EPMC3995462 | biostudies-literature
Project description:Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) causes dramatic reductions in white adipose tissue in mice but has had limited effectiveness in humans. Determination of the signaling pathways involved may lead to better regulation of adiposity. T10c12 CLA was found to activate AMP-activating protein kinase (AMPK), a central regulator of cell metabolism. Compound C, a potent inhibitor of AMPK, prevents many of the typical responses to treatments with t10c12 CLA including the integrated stress response (ISR), the inflammatory response, the reduction in key lipogenic transcription factors, and delipidation. Treatment of adipocytes or mice with t10c12 CLA in conjunction with AMPK activator metformin results in more delipidation than treatment with the individual chemicals. Additionally, the combination showed a reduced inflammatory response relative to a t10c12 CLA treatment alone. The combination of t10c12 CLA and metformin, widely used to treat insulin resistance and Type II diabetes, has potential as a treatment for reducing adiposity in humans. Keywords: control/treatment Mouse 3T3-L1 RNA for was isolated from control linoleic acid (LA) and treatment (CLA, CLA+metformin, metformin) samples for analysis on microarrays with three biological reps.
2009-11-01 | E-GEOD-14888 | biostudies-arrayexpress
Project description:Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) causes dramatic reductions in white adipose tissue in mice but has had limited effectiveness in humans. Determination of the signaling pathways involved may lead to better regulation of adiposity. T10c12 CLA was found to activate AMP-activating protein kinase (AMPK), a central regulator of cell metabolism. Compound C, a potent inhibitor of AMPK, prevents many of the typical responses to treatments with t10c12 CLA including the integrated stress response (ISR), the inflammatory response, the reduction in key lipogenic transcription factors, and delipidation. Treatment of adipocytes or mice with t10c12 CLA in conjunction with AMPK activator metformin results in more delipidation than treatment with the individual chemicals. Additionally, the combination showed a reduced inflammatory response relative to a t10c12 CLA treatment alone. The combination of t10c12 CLA and metformin, widely used to treat insulin resistance and Type II diabetes, has potential as a treatment for reducing adiposity in humans. Keywords: control/treatment
2009-11-01 | GSE14888 | GEO
Project description:The white adipose tissue (WAT) rapidly loses mass when mice are fed a diet containing trans-10, cis-12 conjugated linoleic acid (t10c12 CLA). A microarray analysis of WAT due to CLA feeding was performed to better define the processes and genes involved. WAT weight decreased by ca. 80% over 17 days of feeding a 0.5% t10c12 CLA diet. The lipid volume decreased by 90% and the number of adipocytes and total cells were reduced by15% and 47%, respectively. Microarray profiling of replicated pools of control and treated mice (n=140) at seven time points over the 17day feeding indicated between 2798 to 4318 genes showed mRNA changes of 2-fold or more. Transcript levels for genes of glucose and fatty acid import or biosynthesis were significantly reduced. A prolific inflammation response was indicated by the 2 to100-fold induction of many cytokine transcripts, including those for IL-6, IL1?, TNF ligands, and CXC family members We used microarrays to characterize transcriptome changes in mouse adipose tissue due to feeding trans-10 cis-12 linoleic acid . Keywords: time course
2006-07-28 | GSE4671 | GEO