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JNK inhibitor SP600125 attenuates trans‐10, cis‐12 (10,12) conjugated linoleic acid (CLA)‐ mediated inflammation and suppression of adipogenic and lipogenic genes in human (pre)adipocytes
Author(s) -
Kennedy Arion,
Martinez K.,
West T.,
McIntosh M.
Publication year - 2009
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.23.1_supplement.717.17
Subject(s) - conjugated linoleic acid , adipogenesis , medicine , endocrinology , chemistry , inflammation , adiponectin , insulin resistance , phosphorylation , lipogenesis , kinase , adipose tissue , biochemistry , biology , insulin , fatty acid , linoleic acid
Numerous animal studies and several human studies have demonstrated that supplementation with a mixture of 10,12 and cis‐9, trans‐11 (9,11) isomers of CLA, or 10,12 CLA alone, reduces body weight and fat deposition. Precisely how CLA reduces adiposity remains unclear. We have identified that 10,12 CLA, but not 9,11 CLA, increases the phosphorylation of c‐Jun NH2‐terminal kinase (JNK) in primary cultures of human adipocytes. Thus, we hypothesized that 10,12 CLA‐mediated inflammation, insulin resistance, and delipidation are dependent on JNK activation. To test this hypothesis, cultures were treated with 10,12 CLA in the absence or presence of SP600125. 10,12 CLA‐mediated phosphorylation of JNK was blocked by SP600125. SP600125 attenuated 10,12 CLA‐induction of inflammatory genes, including interleukin (IL)‐6, IL‐8, IL‐1β[double‐underdot), activating transcription factor (ATF)‐3, and cyclooxygenase (COX)‐2 in a dose dependent manner. Similarly, 10,12 CLA suppression of adipogenic/lipogenic genes (i.e, adiponectin, PPARγ, GLUT4, LXRα, SCD‐1, ACC) were attenuated by SP600125. Collectively, these data demonstrate that JNK activation regulates 10,12 CLA induction of inflammatory genes and suppression of adipogenic/lipogenic genes. (Supported by NIH 2R01‐DK063070, NIH F31DK076208, and NCARS 0677.)