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 journalJournal articleResearchpeer-review

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 kappaB (NFkappaB) 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-NH2-terminal kinase (JNK), and induction of inflammatory genes. 10,12 CLA-mediated binding of NFkappaB to the promoters of interleukin (IL)-8 and cyclooxygenase (COX)-2 and induction of calcium-calmodulin kinase II (CaMKII) beta 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 F2alpha, and suppression of peroxisome proliferator activated receptor gamma 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
JournalJournal of Lipid Research
Volume51
Issue number7
Pages (from-to)1906-17
Number of pages12
ISSN0022-2275
DOIs
Publication statusPublished - 1. Jul 2010

Keywords

  • Adipocytes
  • Adult
  • Animals
  • Calcium
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammation
  • Insulin Resistance
  • JNK Mitogen-Activated Protein Kinases
  • Linoleic Acids, Conjugated
  • Mice
  • Middle Aged
  • Mitochondria
  • NF-kappa B
  • Reactive Oxygen Species
  • Type C Phospholipases
  • Young Adult

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