title: Fructose-induced inflammation, insulin resistance and oxidative stress: A liver pathological triad effectively disrupted by lipoic acid.
abstract: OBJECTIVE
  Fructose administration induces hepatic oxidative stress, insulin resistance, inflammatory and metabolic changes. We tested their potential pathogenic relationship and whether these alterations can be prevented by R/S-α-lipoic acid.
  
  
  METHODS
  Wistar rats received during 21days a commercial diet or the same diet supplemented with 10% fructose in drinking water without/with R/S-α-lipoic acid injection. After this period, we measured a) serum glucose, triglyceride, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), insulin glucose ratio (IGR) and Matsuda indexes and b) liver oxidative stress, inflammatory markers and insulin signaling pathway components.
  
  
  RESULTS
  Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR, IGR and lower Matsuda indices compared to control animals, together with increased oxidative stress markers, TNFα, IL1β and PAI-1 gene expression, and TNFα and COX-2 protein content. Whereas insulin receptor level was higher in fructose fed rats, their tyrosine-residue phosphorylation was lower. IRS1/IRS2 protein levels and IRS1 tyrosine-phosphorylation rate were lower in fructose fed rats. All changes were prevented by R/S-α-lipoic acid co-administration.
  
  
  CONCLUSIONS
  Fructose-induced hepatic oxidative stress, insulin resistance and inflammation form a triad that constitutes a vicious pathogenic circle. This circle can be effectively disrupted by R/S-α-lipoic acid co-administration, thus suggesting mutual positive interaction among the triad components.
authors.affiliation: CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Argentina.
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Castro
authors.affiliation: CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Argentina.
authors.forename: María Laura
authors.initials: ML
authors.lastname: Massa
authors.affiliation: CIC, Centro de Investigaciones Cardiovasculares (UNLP-CONICET La Plata), Argentina.
authors.forename: Luisa González
authors.initials: LG
authors.lastname: Arbeláez
authors.affiliation: Farmacología Básica, Facultad de Ciencias Médicas UNLP, La Plata, Argentina.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Schinella
authors.affiliation: CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Argentina.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gagliardino
authors.affiliation: CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Argentina. Electronic address: f_francini@yahoo.com.
authors.forename: Flavio
authors.initials: F
authors.lastname: Francini
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D019587:Dietary Supplements; D005632:Fructose / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000096:biosynthesis; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; C000594089:IL1B protein, rat; D018836:Inflammation Mediators; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D053583:Interleukin-1beta; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D008063:Thioctic Acid; D051546:Cyclooxygenase 2; D011972:Receptor, Insulin
keywords: Fructose-rich diet; Inflammation; Oxidative-stress; Prediabetes; R/S-α-lipoic acid