Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes.
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.
Kennedy
Arion
A
Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC, USA.
Martinez
Kristina
K
Chung
Soonkyu
S
LaPoint
Kathy
K
Hopkins
Robin
R
Schmidt
Soren F
SF
Andersen
Kenneth
K
Mandrup
Susanne
S
McIntosh
Michael
M
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D055815:Young Adult
C094849:10,12-octadecadienoic acid; D044243:Linoleic Acids, Conjugated; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D002118:Calcium