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Inflammation and delipidation induced by trans‐10, cis‐12 conjugated linoleic acid (CLA) is linked to intracellular calcium accumulation in primary cultures of human adipocytes
Author(s) -
Kennedy Arion,
Chung S.,
Hopkins R.,
LaPoint K.,
McIntosh M.
Publication year - 2007
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.21.5.a703-d
Subject(s) - egta , bapta , extracellular , conjugated linoleic acid , chemistry , tumor necrosis factor alpha , calcium in biology , intracellular , cytokine , inflammation , calcium , endocrinology , proinflammatory cytokine , mapk/erk pathway , signal transduction , medicine , microbiology and biotechnology , biochemistry , linoleic acid , biology , fatty acid , organic chemistry
We have demonstrated that trans‐10, cis‐12 CLA (10,12) causes delipidation and secretion of inflammatory cytokines in cultures of newly differentiated human adipocytes by activating nuclear factor κB (NFκB) and extracellular signal related kinase (ERK) 1/2 signaling. Based on the role that intracellular calcium [Ca 2+ ] i plays in regulating cell signaling and lipid metabolism, we hypothesized that [Ca 2+ ] i is an upstream mediator of 10,12 CLA activation of NFκB and ERK1/2 and induction of cytokines. To examine the extent to which 10,12 CLA impacts [Ca 2+ ] i , cultures were preloaded with Fluo‐3 AM and then injected with cis‐9, trans‐11 (9,11) CLA, 10,12 CLA, or vehicle. 10,12 CLA robustly increased [Ca 2+ ] i compared to 9,11 and vehicle. To demonstrate that [Ca 2+ ] i is linked to inflammation, calcium chelators (BAPTA, EGTA) or an inhibitor of [Ca 2+ ] i release (TMB) were utilized. BAPTA and EGTA blocked interleukin (IL)‐6 and tumor necrosis factor (TNF) α gene expression, whereas TMB decreased IL‐6, in cultures treated with 10,12 CLA compared to vehicle. Consistent with these cytokine data, BAPTA and TMB inhibited or attenuated, respectively, the 10,12 CLA‐mediated increase of [Ca 2+ ] i . Collectively, these data suggest that 10,12 CLA activation of NFκB and ERK1/2 and induction of cytokines involves [Ca 2+ ] i accumulation in human adipocytes. NIH‐NIDDK/ODS DK063070, NCARS 06771, F31DK076208‐01, and UNCF‐Merck.