PMID- 18835938
OWN - NLM
STAT- MEDLINE
DCOM- 20090330
LR  - 20181113
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 58
IP  - 1
DP  - 2009 Jan
TI  - Obesity-related upregulation of monocyte chemotactic factors in adipocytes: 
      involvement of nuclear factor-kappaB and c-Jun NH2-terminal kinase pathways.
PG  - 104-15
LID - 10.2337/db07-1344 [doi]
AB  - OBJECTIVE: We sought to evaluate the entire picture of all monocyte chemotactic 
      factors that potentially contribute to adipose tissue macrophage accumulation in 
      obesity. RESEARCH DESIGN AND METHODS: Expression and regulation of members in the 
      entire chemokine superfamily were evaluated in adipose tissue and isolated 
      adipocytes of obese versus lean mice. Kinetics of adipose tissue macrophage 
      infiltration was characterized by fluorescence-activated cell sorting. The 
      effects of fatty acids on stimulation of chemokine expression in adipocytes and 
      underlying mechanisms were investigated. RESULTS: Six monocyte chemotactic 
      factors were found to be predominantly upregulated in isolated adipocytes versus 
      stromal vascular cells in obese mice for the first time, although most of them 
      were previously reported to be upregulated in whole adipose tissue. In 
      diet-induced obese mice, adipose tissue enlargement, increase of adipocyte 
      number, and elevation of multiple chemokine expression precede the initiation of 
      macrophage infiltration. Free fatty acids (FFAs) are found to be inducers for 
      upregulating these chemokines in 3T3-L1 adipocytes, and this effect can be 
      partially blunted by reducing Toll-like receptor 4 expression. FFAs induce 
      expression of monocyte chemotactic factors in adipocytes via both 
      transcription-dependent and -independent mechanisms. In contrast to the reported 
      role of JNK as the exclusive mediator of FFA-induced monocyte chemoattractant 
      protein-1 (MCP-1) expression in macrophages, we show a novel role of inhibitor of 
      kappaB kinase-beta (IKKbeta) in mediating FFA-induced upregulation of all six 
      chemokines and a role of JNK in FFA-induced upregulation of MCP-1 and MCP-3. 
      CONCLUSIONS: Multiple chemokines derived from adipocytes might contribute to 
      obesity-related WAT macrophage infiltration with FFAs as potential triggers and 
      involvement of both IKKbeta and JNK pathways.
FAU - Jiao, Ping
AU  - Jiao P
AD  - Hallett Center for Diabetes and Endocrinology, Brown Medical School, Providence, 
      Rhode Island, USA.
FAU - Chen, Qiu
AU  - Chen Q
FAU - Shah, Suketu
AU  - Shah S
FAU - Du, Jing
AU  - Du J
FAU - Tao, Bo
AU  - Tao B
FAU - Tzameli, Iphigenia
AU  - Tzameli I
FAU - Yan, Weiqun
AU  - Yan W
FAU - Xu, Haiyan
AU  - Xu H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081003
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Chemokines)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Spag9 protein, mouse)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Adipocytes/cytology/drug effects/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokines/genetics
MH  - Fatty Acids, Nonesterified/pharmacology
MH  - Gene Expression/drug effects
MH  - Gene Expression Profiling
MH  - Male
MH  - Mice
MH  - Mice, Obese
MH  - Monocyte Chemoattractant Proteins/*genetics
MH  - NF-kappa B/*genetics
MH  - Obesity/metabolism/*physiopathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects/genetics/physiology
PMC - PMC2606857
EDAT- 2008/10/07 09:00
MHDA- 2009/03/31 09:00
PMCR- 2010/01/01
CRDT- 2008/10/07 09:00
PHST- 2008/10/07 09:00 [pubmed]
PHST- 2009/03/31 09:00 [medline]
PHST- 2008/10/07 09:00 [entrez]
PHST- 2010/01/01 00:00 [pmc-release]
AID - db07-1344 [pii]
AID - 581104 [pii]
AID - 10.2337/db07-1344 [doi]
PST - ppublish
SO  - Diabetes. 2009 Jan;58(1):104-15. doi: 10.2337/db07-1344. Epub 2008 Oct 3.