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Conjugated linoleic acid activates AMPK and reduces adiposity more effectively when used with metformin

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE14888 | GEO | 2009/11/01

SECONDARY ACCESSION(S): PRJNA111955

REPOSITORIES: GEO

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Conjugated linoleic acid activates AMPK and reduces adiposity more effectively when used with metformin

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

Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes

Project description:Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes. Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride levels in adipocytes. AMP-activated protein kinase (AMPK) was recently demonstrated to be involved in the emerging pathways regulating this response. This study investigated the role of AMPK and inflammation in lowering triglyceride levels by testing the following hypotheses: 1) A moderate activator of AMPK, such as metformin, and an inflammatory response are sufficient to reduce triglycerides, and 2) Strong activation of AMPK is also sufficient. These experiments were performed by adding compounds that affect these pathways and measuring their effects in 3T3-L1 adipocytes. Tumor necrosis factor α (TNF-α), an inflammatory cytokine, increased the ability of metformin to reduce triglycerides, but TNF-α was observed to activate AMPK. A comparison of metformin, phenformin, TNF-α, and t10c12 CLA found a correlation between AMPK activity level and triglyceride reduction. Inhibitors of the prostaglandin (PG) biosynthetic pathway interfered with t10c12 CLA's ability to reduce triglycerides. Inhibitors of MAPK/ERK kinase or Jun N-terminal kinase interfered with the phosphorylation of phospholipase A2 and triglyceride reductions. Keywords: control/treatment Mouse 3T3-L1 RNA was isolated from control (LA) and treatment (CLA, phenformin) samples for analysis on microarrays with three biological replicates per sample. Limma data are available in the Supplementary files 'GSE17404_limma_CLAvsLA.txt', 'GSE17404_limma_PFMvsLA.txt', and 'GSE17404_limma_PFMvsCLA.txt'.

2010-08-10 | E-GEOD-17404 | biostudies-arrayexpress

Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes

2010-08-10 | GSE17404 | GEO

Gene expression in 3T3-L1 mouse tissue (preadipocytes) treated with Trans-10,Cis-12 conjugated linoleic acid(t10c12 CLA)

Project description:Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse white adipose tissue (WAT) and 3T3-L1 adipocyte tissue culture; however in preadipocyte tissue (this series) the UPS/ISR and fat loss is not detected. The early transcriptome changes in 3T3-L1 preadipocyte tissue culture were analyzed using high-density microarrays to better characterize the signaling pathways responding to t10c12 CLA. Their gene expression responses between 4 to 12 hr after treatment do not show a set of genes indicative of an integrated stress response (ISR). Keywords: control/treatment time course

2008-01-11 | GSE8683 | GEO

Gene expression in mouse 3T3-L1 adipocyte tissue culture treated with cis-9,trans-11 conjugated linoleic acid(c9t11 CLA)

Project description:Trans-10, Cis-12 conjugated linoleic acid (t10c12 CLA) causes fat loss in mouse 3T3-L1 adipocyte tissue culture; however cis-9, trans-11 CLA does not (this series). The early transcriptome changes were analyzed using high-density microarrays to better characterize the signaling pathways responding to c9t11 CLA. Their gene expression responses between 8 to 12 hr after treatment showed no gene expression changes indicative of an integrated stress response (ISR). Keywords: control/treatment time course

2008-01-11 | GSE8684 | GEO

Transcription profiling of mouse 3T3-L1 tissue (preadipocytes) treated with trans-10,Cis-12 conjugated linoleic acid(t10c12 CLA)

2008-06-16 | E-GEOD-8683 | biostudies-arrayexpress

Microarray Analysis of the Delipidation of White Adipose Tissue of Mice Fed Conjugated Linoleic Acid

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

Transcription profiling of mouse 3T3-L1 adipocyte tissue culture treated with cis-9,trans-11 conjugated linoleic acid(c9t11 CLA)

2008-06-16 | E-GEOD-8684 | biostudies-arrayexpress

Transcription profiling of mouse white adipose tissue from mice fed trans-10, cis-12 conjugated linoleic acid to determine the processes involved in the generated inflammation and de-lipidation of the adipose tissue

2007-11-23 | E-GEOD-4671 | biostudies-arrayexpress

Transcription profiling of mouse adipocytes treated with trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes (GEO Super Series)

Project description:This SuperSeries is composed of the following subset Series:; GSE8679: Gene expression in mouse white adipose tissue; GSE8681: Gene expression in mouse 3T3-L1 adipocyte tissue culture treated with CLA; GSE8682: Gene expression in mouse 3T3-L1 adipocyte tissue culture treated with tunicamycin; GSE8683: Gene expression in 3T3-L1 mouse tissue (preadipocytes) treated with Trans-10,Cis-12 conjugated linoleic acid(t10c12 CLA); GSE8684: Gene expression in mouse 3T3-L1 adipocyte tissue culture treated with cis-9,trans-11 conjugated linoleic acid(c9t11 CLA) Experiment Overall Design: Refer to individual Series

2008-06-20 | E-GEOD-11384 | biostudies-arrayexpress

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