title: Refeeding with glucose rather than fructose elicits greater hepatic inflammatory gene expression in mice.
abstract: OBJECTIVE
  We 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.
  
  
  METHODS
  Mice 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.
  
  
  RESULTS
  Fasting 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.
  
  
  CONCLUSIONS
  Dietary 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.
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Japan. Electronic address: Motoko.o@faculty.chiba-u.jp.
authors.forename: Motoko
authors.initials: M
authors.lastname: Oarada
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Takahashi-Nakaguchi
authors.affiliation: Department of Nutrition, Tokushima University School of Medicine, Tokushima, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Nutrition, Tokushima University School of Medicine, Tokushima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
authors.affiliation: Department of Medical Physiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Gonoi
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics; D000818:Animals; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005215:Fasting / Q000378:metabolism*; D005248:Feeding Methods; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000178:diet therapy / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D012038:Regeneration / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D004040:Dietary Carbohydrates; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D051195:Toll-Like Receptor 2; D005632:Fructose; D000410:Alanine Transaminase; D005947:Glucose
keywords: Acute starvation; Carbohydrate; Glucose; Inflammatory gene expression; Refeeding