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

38 Citations (Scopus)

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

Fingerprint

Conjugated Linoleic Acids
Adipocytes
Insulin Resistance
Insulin
KN 62
Inflammation
Calcium
Calcium-Calmodulin-Dependent Protein Kinases
Endoplasmic Reticulum
Reactive Oxygen Species
Genes
Chemical activation
MAP Kinase Kinase 4
Peroxisome Proliferator-Activated Receptors
Prostaglandins F
Type C Phospholipases
Cyclooxygenase 2
trans-10,cis-12-conjugated linoleic acid
Interleukin-8
Phosphotransferases

Keywords

  • Cell signaling
  • Fatty acid
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes. / Kennedy, Arion; Martinez, Kristina; Chung, Soonkyu; LaPoint, Kathy; Hopkins, Robin; Schmidt, Soren F.; Andersen, Kenneth; Mandrup, Susanne; McIntosh, Michael.

In: Journal of Lipid Research, Vol. 51, No. 7, 01.07.2010, p. 1906-1917.

Research output: Contribution to journalArticle

Kennedy, Arion ; Martinez, Kristina ; Chung, Soonkyu ; LaPoint, Kathy ; Hopkins, Robin ; Schmidt, Soren F. ; Andersen, Kenneth ; Mandrup, Susanne ; McIntosh, Michael. / Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes. In: Journal of Lipid Research. 2010 ; Vol. 51, No. 7. pp. 1906-1917.
@article{0f7b01218a2648c299c530080dbb6150,
title = "Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes",
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 2α, 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.",
keywords = "Cell signaling, Fatty acid, Reactive oxygen species",
author = "Arion Kennedy and Kristina Martinez and Soonkyu Chung and Kathy LaPoint and Robin Hopkins and Schmidt, {Soren F.} and Kenneth Andersen and Susanne Mandrup and Michael McIntosh",
year = "2010",
month = "7",
day = "1",
doi = "10.1194/jlr.M005447",
language = "English (US)",
volume = "51",
pages = "1906--1917",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "7",

}

TY - JOUR

T1 - Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes

AU - Kennedy, Arion

AU - Martinez, Kristina

AU - Chung, Soonkyu

AU - LaPoint, Kathy

AU - Hopkins, Robin

AU - Schmidt, Soren F.

AU - Andersen, Kenneth

AU - Mandrup, Susanne

AU - McIntosh, Michael

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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 2α, 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.

AB - 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 2α, 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.

KW - Cell signaling

KW - Fatty acid

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=77953507643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953507643&partnerID=8YFLogxK

U2 - 10.1194/jlr.M005447

DO - 10.1194/jlr.M005447

M3 - Article

C2 - 20154361

AN - SCOPUS:77953507643

VL - 51

SP - 1906

EP - 1917

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 7

ER -