title: Rat liver uncoupling protein 2: changes induced by a fructose-rich diet.
abstract: OBJECTIVE
  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).
  
  
  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, 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CENEXA – Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET LA PLATA, Centro Colaborador OPS/OMS en Diabetes), Facultad de Ciencias Médicas, Calles 60 y 120, 1900 La Plata, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Castro
authors.forename: María L
authors.initials: ML
authors.lastname: Massa
authors.forename: Héctor
authors.initials: H
authors.lastname: Del Zotto
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gagliardino
authors.forename: Flavio
authors.initials: F
authors.lastname: Francini
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D005632:Fructose / Q000378:metabolism*; D005786:Gene Expression Regulation; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D000071246:Uncoupling Protein 2
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D014280:Triglycerides; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D005632:Fructose