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BMC Physiology

, 10:20

First Online: 19 October 2010Received: 19 September 2009Accepted: 19 October 2010

Abstract

BackgroundObese patients display an exaggerated morbidity during sepsis. Since consumption of a western-style diet WD is a major factor for obesity in the United States, the purpose of the present study was to examine the influence of chronic WD consumption on hepatic inflammation in mice made septic via cecal ligation and puncture CLP. Feeding mice diets high in fat has been shown to enhance evidence of TLR signaling and this pathway also mediates the hepatic response to invading bacteria. Therefore, we hypothesized that the combined effects of sepsis and feeding WD on TRL-4 signaling would exacerbate hepatic inflammation. Male C57BL-6 mice were fed purified control diet CD or WD that was enriched in butter fat 34.4% of calories for 3 weeks prior to CLP. Intravital microscopy was used to evaluate leukocyte adhesion in the hepatic microcirculation. To demonstrate the direct effect of saturated fatty acid on hepatocytes, C3A human hepatocytes were cultured in medium containing 100 μM palmitic acid PA. Quantitative real-time PCR was used to assess mRNA expression of tumor necrosis factor-alpha TNF-α, monocyte chemotactic protein-1 MCP-1, intercellular adhesion molecule-1 ICAM-1, toll-like receptor-4 TLR-4 and interleukin-8 IL-8.

ResultsFeeding WD increased firm adhesion of leukocytes in the sinusoids and terminal hepatic venules by 8-fold six hours after CLP; the increase in platelet adhesion was similar to the response observed with leukocytes. Adhesion was accompanied by enhanced expression of TNF-α, MCP-1 and ICAM-1. Messenger RNA expression of TLR-4 was also exacerbated in the WD+CLP group. Exposure of C3A cells to PA up-regulated IL-8 and TLR-4 expression. In addition, PA stimulated the static adhesion of U937 monocytes to C3A cells, a phenomenon blocked by inclusion of an anti-TLR-4-MD2 antibody in the culture medium.

ConclusionsThese findings indicate a link between obesity-enhanced susceptibility to sepsis and consumption of a western-style diet.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6793-10-20 contains supplementary material, which is available to authorized users.

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Autor: Chantal A Rivera - LaTausha Gaskin - Georg Singer - Jeff Houghton - Monique Allman

Fuente: https://link.springer.com/



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