PMID- 18303122
OWN - NLM
STAT- MEDLINE
DCOM- 20080619
LR  - 20220317
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 294
IP  - 5
DP  - 2008 May
TI  - JNK- and IkappaB-dependent pathways regulate MCP-1 but not adiponectin release 
      from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in 
      vitro.
PG  - E898-909
LID - 10.1152/ajpendo.00131.2007 [doi]
AB  - Obese conditions increase the expression of adipocytokine monocyte 
      chemoattractant protein-1 (MCP-1) in adipose tissue as well as MCP-1 plasma 
      levels. To investigate the mechanism behind increased MCP-1, we used a model in 
      which 3T3-L1 adipocytes were artificially hypertrophied by preloading with 
      palmitate in vitro. As observed in obesity, under our model conditions, 
      palmitate-preloaded cells showed significantly increased oxidative stress and 
      increased MCP-1 expression relative to control cells. This increased MCP-1 
      expression was enhanced by adding exogenous tumor necrosis factor-alpha 
      (TNF-alpha; 17.8-fold vs. control cells, P < 0.01) rather than interleukin-1beta 
      (IL-1beta; 2.6-fold vs. control cells, P < 0.01). However, endogenous TNF-alpha 
      and IL-1beta release was not affected in hypertrophied cells, suggesting that 
      these endogenous cytokines do not mediate hypertrophy-induced increase in MCP-1. 
      MCP-1 secretion from hypertrophied cells was significantly decreased by treatment 
      with antioxidant N-acetyl-cysteine, JNK inhibitors SP600125 and JIP-1 peptide, 
      and IkappaB phosphorylation inhibitors BAY 11-7085 and BMS-345541 (P < 0.01). 
      MCP-1 secretion was not affected by peroxisome proliferator-activated 
      receptor-gamma (PPARgamma) antagonists assayed. Adiponectin, another 
      adipocytokine studied in parallel, also showed increased release in hypertrophy 
      relative to control cells. But in contrast to MCP-1, adiponectin release was 
      significantly suppressed by both exogenous TNF-alpha and IL-1beta as well as by 
      PPARgamma antagonists bisphenol A diglycidyl ether and T0070907 (P < 0.01). JNK 
      inhibitors and IkappaB phosphorylation inhibitors showed no significant effect on 
      adiponectin. We conclude that adipocyte hypertrophy through palmitate loading 
      causes oxidative stress, which in turn increases MCP-1 expression and secretion 
      through JNK and IkappaB signaling. In contrast, the parallel increase in 
      adiponectin expression appears to be related to the PPARgamma ligand properties 
      of palmitate.
FAU - Takahashi, Kazuto
AU  - Takahashi K
AD  - Third Department of Internal Medicine, Kyorin University School of Medicine, 
      Tokyo, Japan.
FAU - Yamaguchi, Shinya
AU  - Yamaguchi S
FAU - Shimoyama, Tatsuhiro
AU  - Shimoyama T
FAU - Seki, Hiroyuki
AU  - Seki H
FAU - Miyokawa, Kaoru
AU  - Miyokawa K
FAU - Katsuta, Hidenori
AU  - Katsuta H
FAU - Tanaka, Toshiaki
AU  - Tanaka T
FAU - Yoshimoto, Katsuhiko
AU  - Yoshimoto K
FAU - Ohno, Hideki
AU  - Ohno H
FAU - Nagamatsu, Shinya
AU  - Nagamatsu S
FAU - Ishida, Hitoshi
AU  - Ishida H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080226
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Adiponectin)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (PPAR gamma)
RN  - 0 (Palmitates)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Adipocytes/drug effects/*metabolism/ultrastructure
MH  - Adiponectin/*metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Cell Size/drug effects
MH  - Chemokine CCL2/*metabolism
MH  - Hydrogen Peroxide/metabolism
MH  - I-kappa B Kinase/*physiology
MH  - Interleukin-1beta/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/*physiology
MH  - Mice
MH  - PPAR gamma/metabolism/physiology
MH  - Palmitates/*pharmacology
MH  - Signal Transduction/*physiology
MH  - Triglycerides/biosynthesis
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2008/02/28 09:00
MHDA- 2008/06/20 09:00
CRDT- 2008/02/28 09:00
PHST- 2008/02/28 09:00 [pubmed]
PHST- 2008/06/20 09:00 [medline]
PHST- 2008/02/28 09:00 [entrez]
AID - 00131.2007 [pii]
AID - 10.1152/ajpendo.00131.2007 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2008 May;294(5):E898-909. doi: 
      10.1152/ajpendo.00131.2007. Epub 2008 Feb 26.