PMID- 27170207
OWN - NLM
STAT- MEDLINE
DCOM- 20170411
LR  - 20220311
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Print)
IS  - 1340-3478 (Linking)
VI  - 23
IP  - 12
DP  - 2016 Dec 1
TI  - AICAR Attenuates TNFalpha-Induced Inappropriate Secretion of Monocyte Chemoattractant 
      Protein-1 and Adiponectin in 3T3-L1 Adipocytes.
PG  - 1345-1354
AB  - AIM: The increase in monocyte chemoattractant protein-1 (MCP-1) and the decrease 
      in adiponectin production from hypertrophic adipocytes are associated with 
      adipose tissue inflammation and its metabolic complications. The aim of this 
      study was to determine whether 5-aminoimidazole-4-carboxamide 
      1-beta-D-ribofuranoside (AICAR), an adenosine monophosphate-activated protein kinase 
      (AMPK) activator, modulates these adipocytokine productions in tumor necrosis 
      factor-alpha (TNFalpha)-treated adipocytes. METHODS: AICAR and/or other reagents were 
      added to the culture medium, and then, TNFalpha was added to fully differentiated 
      3T3-L1 adipocytes. The MCP-1 and adiponectin production in the culture 
      supernatant was measured by ELISA. AMPK, phosphatidylinositol 3-kinase (PI3K), 
      and nuclear factor-kappaB (NF-kappaB) activities were also assayed. RESULTS: Treatment 
      with TNFalpha increased MCP-1 and decreased adiponectin secretion dose-dependently in 
      the 3T3-L1 adipocytes, and AICAR significantly inhibited these TNFalpha-mediated 
      changes. Interestingly, metformin, another AMPK activator, did not have such 
      effects on these adipocytokines. Both the AMPK and PI3K systems in the cells were 
      significantly activated by the AICAR treatment, but the effects of AICAR on 
      adipocytokines were not weakened by the addition of dorsomorphin, an AMPK 
      inhibitor, or LY294002, a PI3K inhibitor. Pyrrolidine dithiocarbamate (PDTC), an 
      NF-kappaB inhibitor, showed protective effects similar to those as AICAR. AICAR, but 
      not metformin, significantly inhibited the TNFalpha-stimulated activation of NF-kappaB, 
      and dorsomorphin did not change AICAR's effect. CONCLUSION: AICAR attenuates the 
      TNFalpha-induced secretion of MCP-1 and adiponectin in 3T3-L1 adipocytes. The 
      observed effects of AICAR seem to be mainly due to the inhibition of NF-kappaB 
      activation rather than the activation of the AMPK pathway, at least in 
      TNFalpha-treated adipocytes.
FAU - Nagahara, Keiko
AU  - Nagahara K
AD  - Department of Pediatrics, Showa University School of Medicine.
FAU - Dobashi, Kazushige
AU  - Dobashi K
FAU - Ishikawa, Takuya
AU  - Ishikawa T
FAU - Nakano, Yuya
AU  - Nakano Y
FAU - Abe, Yoshifusa
AU  - Abe Y
FAU - Tanaka, Daisuke
AU  - Tanaka D
FAU - Itabashi, Kazuo
AU  - Itabashi K
LA  - eng
PT  - Journal Article
DEP - 20160511
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 0 (Adiponectin)
RN  - 0 (Adipoq protein, mouse)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Ribonucleotides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - 3T3-L1 Cells
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Adipocytes/cytology/drug effects/*metabolism
MH  - Adiponectin/*metabolism
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - Ribonucleotides/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC5221497
COIS- We have no conflicts of interest to declare.
EDAT- 2016/05/14 06:00
MHDA- 2017/04/12 06:00
PMCR- 2016/12/01
CRDT- 2016/05/13 06:00
PHST- 2016/05/14 06:00 [pubmed]
PHST- 2017/04/12 06:00 [medline]
PHST- 2016/05/13 06:00 [entrez]
PHST- 2016/12/01 00:00 [pmc-release]
AID - 10.5551/jat.34835 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2016 Dec 1;23(12):1345-1354. doi: 10.5551/jat.34835. Epub 
      2016 May 11.