Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes

Arion Kennedy, Kristina Martinez, Soonkyu Chung, Kathy LaPoint, Robin Hopkins, Soren F. Schmidt, Kenneth Andersen, Susanne Mandrup, Michael McIntosh

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We previously demonstrated that trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) induced inflammation and insulin resistance in primary human adipocytes by activating nuclear factor κB (NFκB) and extracellular signal-related kinase (ERK) signaling. In this study, we demonstrated that the initial increase in intracellular calcium ([Ca2+]i) mediated by 10,12 CLA was attenuated by TMB-8, an inhibitor of calcium release from the endoplasmic reticulum (ER), by BAPTA, an intracellular calcium chelator, and by D609, a phospholipase C (PLC) inhibitor. Moreover, BAPTA, TMB-8, and D609 attenuated 10,12 CLA-mediated production of reactive oxygen species (ROS), activation of ERK1/2 and cJun-NH 2 -terminal kinase (JNK), and induction of inflammatory genes. 10,12 CLA-mediated binding of NFκB to the promoters of interleukin (IL)-8 and cyclooxygenase (COX)-2 and induction of calcium-calmodulin kinase II (CaMKII) β were attenuated by TMB-8. KN-62, a CaMKII inhibitor, also suppressed 10,12 CLA-mediated ROS production and ERK1/2 and JNK activation. Additionally, KN-62 attenuated 10,12 CLA induction of inflammatory and integrated stress response genes, increase in prostaglandin F , and suppression of peroxisome proliferator activated receptor γ protein levels and insulin-stimulated glucose uptake. These data suggest that 10,12 CLA increases inflammation and insulin resistance in human adipocytes, in part by increasing [Ca2+]i levels, particularly calcium from the ER.

Original languageEnglish (US)
Pages (from-to)1906-1917
Number of pages12
JournalJournal of Lipid Research
Volume51
Issue number7
DOIs
StatePublished - Jul 1 2010

Keywords

  • Cell signaling
  • Fatty acid
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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