Rat liver uncoupling protein 2: Changes induced by a fructose-rich diet

• DOI: 10.1016/j.lfs.2011.07.024
• Publication Date: 2011-08-13T18:01:14Z
• Authors: María C. Castro; María L. Massa; Héctor Del Zotto; Juan J. Gagliardino; Flavio Francini
• Keywords: Blood Glucose; Male; 0301 basic medicine; 2. Zero hunger; Peroxisome Proliferator-Activated Receptors; Fructose; Ion Channels; Diet; Rats; Mitochondrial Proteins; 03 medical and health sciences; Gene Expression Regulation; Liver; Animals; Insulin; Uncoupling Protein 2; Insulin Resistance; Rats, Wistar; Triglycerides

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).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, PPARα, PPARδ and PPARγ 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.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 PPARδ gene and protein expression increased in these animals; PPARγ levels were lower and those of PPARα remained unchanged. FRD also increased the mRNA expression of PPARδ target genes FAS and GPAT.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, PPARδ 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.