期刊
LIFE SCIENCES
卷 89, 期 17-18, 页码 609-614出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2011.07.024
关键词
Fructose-rich diet; Liver uncoupling protein 2; Peroxisome proliferator-activated receptors regulation; Glycoxidative stress
资金
- CONICET
- Universidad Nacional de La Plata, Argentina
Aim: To evaluate the role of uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptors (PPARs) in the response of liver to glycoxidative stress triggered by administration of a fructose-rich diet (FRD). Main methods: We assessed blood glucose in the fasting state and after a glucose load (glucose-oxidase method), serum triglyceride (enzymatic measurement), insulin (radioimmunoassay), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (colorimetric kits) in control and FRD animals. In liver, we measured UCP2, PPAR alpha. PPAR delta and PPAR gamma gene (real-time PCR) and protein (Western blot) expression, fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) gene expression, as well as triglyceride content. Key findings: Blood glucose, serum insulin and triglyceride levels, homeostasis model assessment of insulin resistance (HOMA-IR) indexes and impaired glucose tolerance were higher in FRD rats. Whereas UCP2 and PPAR delta gene and protein expression increased in these animals: PPAR gamma levels were lower and those of PPAR alpha remained unchanged. FRD also increased the mRNA expression of PPAR delta target genes FAS and GPAT. Significance: Our results suggest that a) the increased UCP2 gene and protein expression measured in FRD rats could be part of a compensatory mechanism to reduce reactive oxygen species production induced by the fructose overload, and b) PPARs expression participates actively in the regulation of UCP2 expression, and under the metabolic condition tested, PPAR delta played a key role. This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced glycoxidative stress, and to develop appropriate prevention strategies in obesity and type 2 diabetes. (C) 2011 Elsevier Inc. All rights reserved.
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