ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 OC3.4

Fatty acid-induced induction of TLR-4/NF[kappa]B-pathway in adipocytes links nutritional signaling with innate immunity

Andreas Schäffler, Philipp Gross, Roland Büttner, Cornelius Bollheimer, Christa Büchler, Markus Neumeier, Andrea Kopp, Juergen Schölmerich & Werner Falk

Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.

Objectives: To study the direct effects of fatty acids (FA) and the involvement of the TLR-4/NFκB pathway with respect to the secretion of adipokines and chemokines from adipocytes.

Research design and methods: 3T3-L1 adipocytes were stimulated with increasing doses of FA. The secretion of adiponectin, resistin and MCP-1 was measured by ELISA. NFκB p65 nuclear translocation and TLR-4 expression were investigated by Western blot analysis. NFκB-mediated effects were tested by a specific NFκB-inhibitor. TLR-4-induced effects were analyzed by using a neutralizing TLR-4 antibody. The mRNA expression of adipokines in abdominal adipose tissue of rats fed a standard chow or a high fat diet was investigated by quantitative real time RT-PCR.

Results: FA are capable of stimulating adiponectin and resistin secretion. Concerning MCP-1 secretion, FA exert class-specific and differential effects. TLR-4 is induced during adipocyte differentiation and its expression is enhanced following fatty acid stimulation. The stimulatory effects of stearic and palmitic acid on MCP-1 secretion and of palmitoleic acid on resistin secretion are mediated via NFκB as demonstrated by using a soluble NFκB inhibitor. The stimulatory effects of stearic, palmitic and palmitoleic acid on resistin secretion and the stimulatory effect of stearic acid on MCP-1 secretion are mediated via TLR-4 as demonstrated by using a neutralizing TLR4 antibody. Adipose tissue mRNA expression and serum levels of adipokines did not differ in rats fed a high fat diet.

Conclusions: TLR-4 is induced during adipocyte differentiation and in response to stimulation with FA. FA can activate TLR-4 signaling and subsequent NFκB-activation in order to regulate adipokine and chemokine secretion from adipocytes. The present data provide a new molecular mechanism by which FA can link nutrition with innate immunity in a paracrine or autocrine manner.