Western diet enhances hepatic inflammation in mice exposed to cecal ligation and puncture
| Autor: | Chantal A. Rivera, Jeff Houghton, LaTausha Gaskin, Monique Allman, Georg Singer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Physiology Inflammation Biology lcsh:Physiology Hepatitis Sepsis 03 medical and health sciences Cecum Mice 0302 clinical medicine Internal medicine Physiology (medical) medicine Animals Humans Interleukin 8 Ligation Chemokine CCL2 030304 developmental biology 2. Zero hunger 0303 health sciences lcsh:QP1-981 Tumor Necrosis Factor-alpha Monocyte Fatty Acids Interleukin-8 General Medicine medicine.disease Intercellular Adhesion Molecule-1 Diet Mice Inbred C57BL Toll-Like Receptor 4 Disease Models Animal medicine.anatomical_structure Endocrinology Liver 030220 oncology & carcinogenesis Saturated fatty acid Immunology Tumor necrosis factor alpha medicine.symptom Intravital microscopy Research Article |
| Zdroj: | BMC Physiology BMC Physiology, Vol 10, Iss 1, p 20 (2010) |
| ISSN: | 1472-6793 |
| Popis: | Background Obese 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). Results Feeding 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. Conclusions These findings indicate a link between obesity-enhanced susceptibility to sepsis and consumption of a western-style diet. |
| Databáze: | OpenAIRE |
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