کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6096905 | 1209877 | 2008 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Obesity-Induced Lymphocyte Hyperresponsiveness to Chemokines: A New Mechanism of Fatty Liver Inflammation in Obese Mice
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
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چکیده انگلیسی
Background & Aims: Hepatic lipid retention (steatosis) predisposes hepatitis. We investigated the mechanisms of lymphocyte homing to fatty liver and the role of lipopolysaccharide (LPS) in the onset of inflammation in ob/ob mice. Methods: We decreased intestinal bacterial compounds by oral antibiotic treatment to test the role of endogenous LPS in liver inflammation. Adoptive transfer of lymphocytes was used to study the respective contributions of steatosis and lymphocytes to liver inflammation. We tested lymphocyte response to chemokines by in vitro chemotaxis assays in ob/ob, their lean controls, and “non-obese ob/ob” mice, generated by controlling caloric intake to distinguish between the effects of obesity and leptin deficiency. Results: Antibiotic treatment decreased liver infiltration with CD4+ T, CD8+ T, natural killer (NK)T, B, and NK cells. Adoptive transfer of lymphocytes from ob/ob or control mice showed that (1) steatosis increased lymphocyte recruitment to the liver; (2) CD4+ T, CD8+ T, and B cells from ob/ob mice had a greater propensity to migrate specifically to the liver. This migration was enhanced by LPS. These results were also observed in a model of high-fat diet-induced obesity. CD4+ T and B cells were hyperresponsive to CXCL12 and CXCL13, respectively. Weight normalization in “non-obese ob/ob” mice decreased liver inflammation, lymphocyte response to chemokines, and homing to the liver. Conclusions: Our study provides the first evidence that liver inflammation in mice with genetic or diet-induced obesity results from both steatosis and lymphocyte hyperresponsiveness to chemokines expressed in the liver. These abnormalities are reversible with weight normalization.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 134, Issue 5, May 2008, Pages 1459-1469.e2
Journal: Gastroenterology - Volume 134, Issue 5, May 2008, Pages 1459-1469.e2
نویسندگان
Amélie E. Bigorgne, Laurence Bouchet-Delbos, Sylvie Naveau, Ibrahim Dagher, Sophie Prévot, Ingrid Durand-Gasselin, Jacques Couderc, Philippe Valet, Dominique Emilie, Gabriel Perlemuter,