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The Phospholipase C (PLC) Inhibitor U73122 Inhibits Trans‐10, cis‐12 Conjugated Linoleic Acid (CLA)‐Mediated Inflammatory Signaling and Insulin Resistance in Human Adipocytes
Author(s) -
Shen Wan,
Martinez Kristina,
Chuang Chia Chi,
Overman Angel,
Mcintosh Michael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.585.2
Our lab has shown that CLA increases intracellular calcium, inflammation, and insulin resistance in human primary adipocytes, which is consistent with the actions of diacylglycerol and inositol triphosphate from PLC‐dependent cell signaling. Thus, we hypothesized that PLC is an upstream activator of these cellular responses to CLA. To test this hypothesis, cultures were pretreated with U73122, a universal PLC inhibitor, followed by CLA treatment for 18–48 h. U73122 prevented CLA‐induced gene expression of Ca 2+/ calmodulin‐dependent protein kinase‐β, cyclooxygenase‐2, monocyte chemoattractant protein‐1, interleukin (IL)‐6, and IL8, as well as IL‐6 and IL8 secretion. Consistent with these data, U73122 attenuated CLA‐mediated activation of extracellular signal‐related kinase, c‐Jun N‐terminal kinase, and c‐Jun, an activator protein‐1 transcription factor. U73122 also attenuated CLA‐suppression of 1) the mRNA levels of peroxisome proliferator‐activated receptor (PPAR)‐γ, insulin‐stimulated glucose transporter‐4, acetyl‐CoA carboxylase‐1, and stearoyl‐CoA desaturase‐1, 2) PPAR‐γ protein level, and 3) insulin‐stimulated glucose uptake. Taken together, these data suggest that PLC plays an important role in CLA‐mediated activation inflammation and insulin resistance. Supported by NIH DK‐ODS 5R01 DK063070‐07, NCARS 06771. Grant Funding Source : NIH NIDDK‐ODS 5R01 DK063070 ‐ 07, NCARS 06771