A potential dietary therapeutic approach for Non Alcoholic Fatty Liver Disease

INZAUGARAT, ME; LAZIC M; BILLORDO LA; DARUICH, JORGE; SEARS D.; E. GONZALEZ BALLERGA; FELDSTEIN A; SORDA JA; A. C. CHERÑAVSKY

Los Cocos, Cordoba

Congreso; LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Introduction: Western diet, enriched in £s-6 fatty acids, contributes to development of inflammation in non alcoholic fatty liver diseases (NAFLD). The role of T cells in NAFLD is beginning to be unraveled. CCR7 regulates trafficking and homing of T cells. Lack of CCR7 expression results in accumulation of T Cells in tissues and immediate effector function. Objectives: To evaluate surface CCR7 expression in peripheral and intrahepatic T cells, CCL20 and Th1 related transcripts in the liver of patients with NAFLD. To counteract liver inflammation by feeding mice with diet enriched in £s-3 fatty acids. Methods: Peripheral blood mononuclear cells (PBMC) and liver biopsies were obtained from adults with NAFLD (NAFLD, n=20) or metabolically healthy individuals (Co, n=15). C57BL/6 mice (n=20) were fed either with high fat diet (HFD) with high ratio £s6/£s3 (HFDH) or HFD with low ratio £s6/£s3 (HFDL). PMBC or liver cell suspensions were stained with anti-CD4 or -CD8/anti-CCR7 mAbs and analyzed by Flow Cytometry. An index (ICCR7) was calculated as % (CCR7+/CCR7-) within CD4+ o CD8+cells. mRNA expression of IFN-?×, CCL20, CCL19, CCR7 and T-bet in NAFLD, Co and mice was analyzed by Real-Time PCR. Fold-change values were calculated using the 2-£G£Gt method. Mann-Whitney test was used. Results: % CD4+ infiltrate was augmented in liver of NAFLD related to Co (p=0.030). ICCR7 was lower in intrahepatic CD4+ and CD8+(p=0.007 y p=0.004, respectively) and peripheral CD4+ and CD8+(p=0.007 y p=0.004, respectively) in NAFLD compared to Co. An increased mRNA expression of IFN-?× (p=0.008), T-bet (p<0.001) and CCL20 (p=0.012) was found in NAFLD related to Co. HFDL counteracted the increased expression of IFN-?× (p<0.05), CCL20 (p<0.05), CCL19 (p<0.05) and the lower expression of CCR7 (p<0.05) observed in HFDH fed mice. Conclusions: A preferential recruitment of CCR7- and Th1 differentiation are observed in NAFLD liver. The progression of NAFLD maybe counteracted by a dietary therapeutic approach.