Fructose-induced inflammation, insulin resistance and oxidative stress: A liver pathological triad effectively disrupted by lipoic acid

Life Sci. 2015 Sep 15;137:1-6. doi: 10.1016/j.lfs.2015.07.010. Epub 2015 Jul 17.

Abstract

Aims: 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.

Main 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.

Key findings: 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.

Significance: 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.

Keywords: Fructose-rich diet; Inflammation; Oxidative-stress; Prediabetes; R/S-α-lipoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Blood Glucose / metabolism
  • Cyclooxygenase 2 / biosynthesis
  • Dietary Supplements
  • Fructose / adverse effects*
  • Gene Expression / drug effects
  • Inflammation / blood
  • Inflammation / chemically induced
  • Inflammation / diet therapy*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Insulin / blood
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance* / genetics
  • Interleukin-1beta / biosynthesis
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Rats
  • Rats, Wistar
  • Receptor, Insulin / biosynthesis
  • Thioctic Acid / pharmacology*
  • Thioctic Acid / therapeutic use*
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antioxidants
  • Blood Glucose
  • IL1B protein, rat
  • Inflammation Mediators
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Interleukin-1beta
  • Irs1 protein, rat
  • Irs2 protein, rat
  • Plasminogen Activator Inhibitor 1
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Fructose
  • Thioctic Acid
  • Cyclooxygenase 2
  • Receptor, Insulin