• Motoko Oarada, Azusa Takahashi-Nakaguchi, Tomoki Abe, Takeshi Nikawa, Takashi Miki, and Tohru Gonoi.
• Medical Mycology Research Center, Chiba University, Chiba, Japan. Electronic address: Motoko.o@faculty.chiba-u.jp.
• Nutrition. 2015 May 1;31(5):757-65.

ObjectiveWe previously reported that refeeding after a 48-h fast, used as a study model of starvation and refeeding, promotes acute liver inflammatory gene expression, which is at least partly mediated by toll-like receptor 2 (TLR2). We also previously demonstrated that dietary carbohydrates play critical roles in this process. The aim of this study was to compare the outcomes of refeeding with different carbohydrate sources.MethodsMice were fasted for 46 h and then refed with 1.5% (w/w) agar gel containing 19% carbohydrate (sources: α-cornstarch, glucose, sucrose, or fructose). The liver expression of inflammatory and other specific genes was then sequentially measured for the first 14 h after refeeding initiation.ResultsFasting for 46 h up-regulated the liver expression of endogenous ligands for TLRs (HspA5, Hsp90 aa1, and Hspd1). Refeeding with agar gel containing α-cornstarch or glucose increased the liver expression of Tlr2, proinflammatory genes (Cxcl2, Cxcl10, Cxcl1, Nfkb1, Nfkb2, RelB, Sectm1α, Il1β), stress response genes (Atf3, Asns, Gadd45 a, Perk, Inhbe), detoxification genes (Hmox1, Gsta1, Abca8b), genes involved in tissue regeneration (Gdf15, Krt23, Myc, Tnfrsf12a, Mthfd2), and genes involved in tumor suppression (p53, Txnrd1, Btg2). This refeeding also moderately but significantly elevated the serum levels of alanine aminotransferase. These effects were attenuated in mice refed with agar gel containing sucrose or fructose.ConclusionDietary glucose, rather than fructose, plays a critical role in refeeding-induced acute liver inflammatory gene expression and moderate hepatocyte destruction. Further studies are recommended regarding the role of these effects in liver inflammation and, consequently, liver dysfunction.Copyright © 2015 Elsevier Inc. All rights reserved.

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