PMID- 23264678
OWN - NLM
STAT- MEDLINE
DCOM- 20130903
LR  - 20240513
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 54
IP  - 3
DP  - 2013 Mar
TI  - Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic 
      acid-mediated inflammation in human adipocytes.
PG  - 662-670
LID - S0022-2275(20)41931-5 [pii]
LID - 10.1194/jlr.M031211 [doi]
AB  - Diacylglycerol kinases (DGK) convert diacylglycerol to phosphatidic acid, which 
      has been reported to stimulate calcium release from the endoplasmic reticulum. 
      Based on our published data showing that trans-10, cis-12 conjugated linoleic 
      acid (t10,c12 CLA)-mediated intracellular calcium accumulation is linked to 
      inflammation and insulin resistance, we hypothesized that inhibiting DGKs with 
      R59022 would prevent t10,c12 CLA-mediated inflammatory signaling and insulin 
      resistance in human adipocytes. Consistent with our hypothesis, R59022 attenuated 
      t10,c12 CLA-mediated i) increased gene expression and protein secretion of 
      interleukin (IL)-8, IL-6, and monocyte chemoattractant protein-1 (MCP-1); ii) 
      increased activation of extracellular signal-related kinase (ERK), 
      cJun-NH2-terminal kinase (JNK), and cJun; iii) increased intracellular calcium 
      levels; iv) suppressed mRNA or protein levels of peroxisome proliferator 
      activated receptor gamma, adiponectin, and insulin-dependent glucose transporter 4; 
      and v) decreased fatty acid and glucose uptake and triglyceride content. DGKeta was 
      targeted for investigation based on our findings that i) DGKeta was highly 
      expressed in primary human adipocytes and time-dependently induced by t10,c12 CLA 
      and that ii) t10,c12 CLA-induced DGKeta expression was dose-dependently decreased 
      with R59022. Small interfering RNA (siRNA) targeting DGKeta decreased t10,c12 
      CLA-induced DGKeta, IL-8, and MCP-1 gene expression, as well as activation of JNK 
      and cJun. Taken together, these data suggest that DGKs mediate, in part, t10,c12 
      CLA-induced inflammatory signaling in primary human adipocytes.
FAU - Martinez, Kristina
AU  - Martinez K
AD  - Department of Nutrition, University of North Carolina at Greensboro, Greensboro, 
      NC.
FAU - Shyamasundar, Shruthi
AU  - Shyamasundar S
AD  - Department of Nutrition, University of North Carolina at Greensboro, Greensboro, 
      NC.
FAU - Kennedy, Arion
AU  - Kennedy A
AD  - Department of Molecular Physiology, Vanderbilt University Medical Center, 
      Nashville, TN.
FAU - Chuang, Chia Chi
AU  - Chuang CC
AD  - Department of Nutrition, University of North Carolina at Greensboro, Greensboro, 
      NC.
FAU - Marsh, Angel
AU  - Marsh A
AD  - Department of Nutrition, University of North Carolina at Greensboro, Greensboro, 
      NC.
FAU - Kincaid, Jennifer
AU  - Kincaid J
AD  - Department of Nutrition, University of North Carolina at Greensboro, Greensboro, 
      NC.
FAU - Reid, Tanya
AU  - Reid T
AD  - Department of Nutrition, University of North Carolina at Greensboro, Greensboro, 
      NC.
FAU - McIntosh, Michael
AU  - McIntosh M
AD  - Department of Nutrition, University of North Carolina at Greensboro, Greensboro, 
      NC.
LA  - eng
GR  - F31 DK084812/DK/NIDDK NIH HHS/United States
GR  - R01 DK063070/DK/NIDDK NIH HHS/United States
GR  - 5F31-DK-076208/DK/NIDDK NIH HHS/United States
GR  - 5R01-DK-063070-9/DK/NIDDK NIH HHS/United States
GR  - F31 DK076208/DK/NIDDK NIH HHS/United States
GR  - F31-DK-084812/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121222
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Linoleic Acids, Conjugated)
RN  - 0 (Pyrimidinones)
RN  - 0 (Thiazoles)
RN  - 93076-89-2 (R 59022)
RN  - EC 2.7.1.107 (Diacylglycerol Kinase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adipocytes/*drug effects/*metabolism
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Diacylglycerol Kinase/*antagonists & inhibitors/genetics/metabolism
MH  - Enzyme Inhibitors
MH  - Humans
MH  - Inflammation/chemically induced/*metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Linoleic Acids, Conjugated/*pharmacology
MH  - Pyrimidinones/*pharmacology
MH  - Thiazoles/*pharmacology
PMC - PMC3617941
EDAT- 2012/12/25 06:00
MHDA- 2013/09/04 06:00
PMCR- 2014/03/01
CRDT- 2012/12/25 06:00
PHST- 2012/12/25 06:00 [entrez]
PHST- 2012/12/25 06:00 [pubmed]
PHST- 2013/09/04 06:00 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - S0022-2275(20)41931-5 [pii]
AID - m031211 [pii]
AID - 10.1194/jlr.M031211 [doi]
PST - ppublish
SO  - J Lipid Res. 2013 Mar;54(3):662-670. doi: 10.1194/jlr.M031211. Epub 2012 Dec 22.