Fatty acid-induced induction of Toll-like receptor-4/nuclear factor-kappa B pathway in adipocytes links nutritional signalling with innate immunity

Schaeffler, Andreas and Gross, Philipp and Buettner, Roland and Bollheimer, Cornelius and Buechler, Christa and Neumeier, Markus and Kopp, Andrea and Schoelmerich, Juergen and Falk, Werner (2009) Fatty acid-induced induction of Toll-like receptor-4/nuclear factor-kappa B pathway in adipocytes links nutritional signalling with innate immunity. IMMUNOLOGY, 126 (2). pp. 233-245. ISSN 0019-2805, 1365-2567

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Abstract

To study the effects of fatty acids and the involvement of the Toll-like receptor-4/nuclear factor-kappa B (TLR-4/NF-kappa B) 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-kappa B p65 nuclear translocation and TLR-4 expression were investigated by Western blot. The effects mediated by NF-kappa B were tested using a specific NF-kappa B-inhibitor and TLR-4-induced effects were analysed with a neutralizing TLR-4 antibody. Binding of C-14-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-kappa B. 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.

Item Type: Article
Uncontrolled Keywords: MONOCYTE CHEMOATTRACTANT PROTEIN-1; CONJUGATED LINOLEIC-ACID; ADIPOSE CELL LINE; INSULIN-RESISTANCE; METABOLIC SYNDROME; GENE-EXPRESSION; INFLAMMATORY CHANGES; RECEPTOR EXPRESSION; ADIPONECTIN; OBESITY; adipocyte; adipokines; fatty acids; innate immunity; metabolism; Toll-like receptor-4
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Oct 2020 05:29
Last Modified: 07 Oct 2020 05:29
URI: https://pred.uni-regensburg.de/id/eprint/29518

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