PMID- 18624726
OWN - NLM
STAT- MEDLINE
DCOM- 20090410
LR  - 20220408
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 126
IP  - 2
DP  - 2009 Feb
TI  - Fatty acid-induced induction of Toll-like receptor-4/nuclear factor-kappaB 
      pathway in adipocytes links nutritional signalling with innate immunity.
PG  - 233-45
LID - 10.1111/j.1365-2567.2008.02892.x [doi]
AB  - To study the effects of fatty acids and the involvement of the Toll-like 
      receptor-4/nuclear factor-kappaB (TLR-4/NF-kappaB) pathway with respect to the 
      secretion of adipokines from adipocytes 3T3-L1 adipocytes were stimulated with 
      increasing doses of fatty acids. The secretion of adiponectin, resistin and 
      monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked 
      immunosorbent assay. The NF-kappaB p65 nuclear translocation and TLR-4 expression 
      were investigated by Western blot. The effects mediated by NF-kappaB were tested 
      using a specific NF-kappaB-inhibitor and TLR-4-induced effects were analysed with 
      a neutralizing TLR-4 antibody. Binding of (14)C-labelled fatty acids to 
      TLR-4/MD-2 was investigated using a FLAG-tagged extracellular part of TLR-4 fused 
      to full-length MD-2 via a linker (lipopolysaccharide-Trap). The messenger RNA 
      (mRNA) expression of adipokines in abdominal adipose tissue of rats fed a 
      standard chow or a high-fat diet was investigated by reverse 
      transcription-polymerase chain reaction. The TLR-4 is induced during adipocyte 
      differentiation and its expression is enhanced following fatty acid stimulation. 
      The stimulatory effects of stearic and palmitic acids on MCP-1 secretion and of 
      palmitoleic acid on resistin secretion are mediated via NF-kappaB. The 
      stimulatory effects of stearic, palmitic and palmitoleic acids on resistin 
      secretion and the stimulatory effect of stearic acid on MCP-1 secretion are 
      mediated via TLR-4. Fatty acid-mediated effects are caused by an endogenous 
      ligand because fatty acids were shown not to bind directly to TLR-4/MD-2. Adipose 
      tissue mRNA expression and serum levels of adipokines did not differ in rats fed 
      a high-fat diet. These data provide a new molecular mechanism by which fatty 
      acids can link nutrition with innate immunity.
FAU - Schaeffler, Andreas
AU  - Schaeffler A
AD  - Department of Internal Medicine I, Regensburg University Hospital, Regensburg, 
      Germany. andreas.schaeffler@klinik.uni-regensburg.de
FAU - Gross, Philipp
AU  - Gross P
FAU - Buettner, Roland
AU  - Buettner R
FAU - Bollheimer, Cornelius
AU  - Bollheimer C
FAU - Buechler, Christa
AU  - Buechler C
FAU - Neumeier, Markus
AU  - Neumeier M
FAU - Kopp, Andrea
AU  - Kopp A
FAU - Schoelmerich, Juergen
AU  - Schoelmerich J
FAU - Falk, Werner
AU  - Falk W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080623
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Adiponectin)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dietary Fats)
RN  - 0 (Fatty Acids)
RN  - 0 (NF-kappa B)
RN  - 0 (Resistin)
RN  - 0 (Retn protein, rat)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Abdominal Fat/metabolism
MH  - Adipocytes/*drug effects/immunology/metabolism
MH  - Adiponectin/metabolism
MH  - Animal Nutritional Physiological Phenomena/*immunology
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Diet
MH  - Dietary Fats/administration & dosage
MH  - Fatty Acids/metabolism/*pharmacology
MH  - Immunity, Innate/physiology
MH  - Male
MH  - NF-kappa B/antagonists & inhibitors/*biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Resistin/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Signal Transduction/immunology
MH  - Toll-Like Receptor 4/antagonists & inhibitors/*biosynthesis
PMC - PMC2632685
EDAT- 2008/07/16 09:00
MHDA- 2009/04/11 09:00
PMCR- 2010/02/01
CRDT- 2008/07/16 09:00
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2009/04/11 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
PHST- 2010/02/01 00:00 [pmc-release]
AID - IMM2892 [pii]
AID - 10.1111/j.1365-2567.2008.02892.x [doi]
PST - ppublish
SO  - Immunology. 2009 Feb;126(2):233-45. doi: 10.1111/j.1365-2567.2008.02892.x. Epub 
      2008 Jun 23.