Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8337379 | The Journal of Nutritional Biochemistry | 2013 | 10 Pages |
Abstract
Unhealthy eating behaviors increase the risk of metabolic diseases, but the underlying mechanisms are not fully elucidated. Because inflammation contributes to the pathogenesis of metabolic diseases, it is important to understand the effects of unhealthy eating on the inflammatory state. The objective of our present study was to address the effects of a fasting-refeeding regime, a model of irregular eating, on the hepatic inflammatory responses in mouse. The animals were fasted for 48 h and then refed either a standard or low-carbohydrate/high-fat diet. Inflammatory gene expression in the liver was then sequentially measured for the first 17 h after initiation of refeeding. To assess the roles of dietary carbohydrates and toll-like receptor 2 (TLR2) in the refeeding-induced inflammatory changes, gene expression levels in mice refed only carbohydrates (α-corn starch and sucrose) at different doses and in TLR2-deficient mice refed a standard diet were also analyzed. Refeeding with a standard diet increased the liver expression of Tlr2, proinflammatory mediators (Cxcl10, Cxcl1, Cxcl2, Icam-1) and negative regulators of TLR-signaling (A20 and Atf3). These increases were attenuated in mice refed a low-carbohydrate/high-fat diet. Refeeding only α-corn starch and sucrose also increased the expression of these inflammatory pathway genes depending on the doses. TLR2 deficiency significantly attenuated the refeeding-induced increase in the liver expression of Cxcl10, Cxcl1, Icam-1 and A20. These findings suggest that an irregular eating behavior can elicit a liver inflammatory response, which is at least partly mediated by TLR2, and that dietary carbohydrates play critical roles in this process.
Keywords
NF-κBHMGB1ATF3CXCLTLRGRP94A20GLUT2ALTRefeedingICAM-1GAPDHHSPD1ASTAspartate aminotransferaseAlanine aminotransferasetumor necrosis factor-αToll-like receptorFastingTNF-αnuclear factor κBactivating transcription factor 3chemokine (C-X-C motif) ligand Endogenous ligandintercellular adhesion molecule-1Inflammatory mediatorglucose-regulated protein 94High mobility group box 1Carbohydrateglucose transporter 2glyceraldehydes-3-phosphate dehydrogenaseToll-like receptor 2
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Authors
Motoko Oarada, Takashi Miki, Shohei Kohno, Kanae Sakai, Takeshi Nikawa, Mitsutoshi Yoneyama, Tohru Gonoi,