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

ABSTRACT: 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'.

ORGANISM(S): Mus musculus

SUBMITTER: Jean-Jack Riethoven 

PROVIDER: E-GEOD-17404 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress