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

CASTRO MC; MASSA ML; GONZÁLEZ ARBELÁES L; SCHINELLA G; GAGLIARDINO JJ; FRANCINI F

LIFE SCIENCES

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2015 vol. 137 p. 1 - 6

0024-3205

Aims: Fructose administration induces hepatic oxidativestress, insulin resistance, inflammatory and metabolic changes. We tested theirpotential pathogenic relationship and whether these alterations can beprevented by R/S-α-lipoic acid.  Main methods: Wistar rats received during 21 days a commercialdiet or the same diet supplemented with 10% fructose in drinking water without/withR/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, inflammatorymarkers and insulin signaling pathway components. Key findings: Fructose fed rats had hyperinsulinemia,hypertriglyceridemia, higher HOMA-IR, IGR and lower Matsuda indices compared tocontrol animals, together with increased oxidative stress markers, TNFα, IL1βand PAI-1 gene expression, and TNFα and COX-2 protein content. Whereas insulinreceptor level was higher in fructose fed rats, their tyrosine-residuesphosphorylation was lower. IRS1/IRS2 protein levels and IRS1 tyrosine-phosphorylationrate were lower in fructose fed rats. All changes were prevented byR/S-α-lipoic acid co-administration. Significance: Fructose-induced hepatic oxidative stress,insulin resistance and inflammation form a triad that constitutes a viciouspathogenic circle. This circle can be effectively disrupted by R/S-α-lipoicacid co-administration, thus suggesting mutual positive interaction among thetriad components.