Format

Send to

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

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

Author information

1
CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Argentina.
2
CIC, Centro de Investigaciones Cardiovasculares (UNLP-CONICET La Plata), Argentina.
3
Farmacología Básica, Facultad de Ciencias Médicas UNLP, La Plata, Argentina.
4
CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Argentina. Electronic address: f_francini@yahoo.com.

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

PMID:
26188590
DOI:
10.1016/j.lfs.2015.07.010
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center