期刊
LIFE SCIENCES
卷 137, 期 -, 页码 1-6出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2015.07.010
关键词
Fructose-rich diet; Prediabetes; Inflammation; Oxidative-stress; R/S-alpha-lipoic acid
资金
- CONICET [PIP 2011-0371]
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-alpha-lipoic acid. Main methods: Wistar rats received during 21 days a commercial diet or the same diet supplemented with 10% fructose in drinking waterwithout/with R/S-alpha-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, TNF alpha, IL1 beta and PAI-1 gene expression, and TNF alpha 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-alpha-lipoic acid co-administration. Significance: Fructose-induced hepatic oxidative stress, insulin resistance and inflammation forma triad that constitutes a vicious pathogenic circle. This circle can be effectively disrupted by R/S-alpha-lipoic acid co-administration, thus suggesting mutual positive interaction among the triad components. (C) 2015 Elsevier Inc. All rights reserved.
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