title: Overproduction of altered VLDL in an insulin-resistance rat model: Influence of SREBP-1c and PPAR-α.
abstract: BACKGROUND
  In insulin-resistance, VLDL presents alterations that increase its atherogenic potential. The mechanism by which insulin-resistance promotes the production of altered VLDL is still not completely understood. The aim of this study was to evaluate the relationship between the expression of sterol regulatory element binding protein 1c (SREBP-1c) and of peroxisome proliferator-activated receptor-α (PPAR-α), with the features of composition and size of VLDL in an insulin-resistance rat model induced by a sucrose rich diet (SRD).
  
  
  METHODS
  The study was conducted on 12 male Wistar rats (180g) receiving SRD (12 weeks) and 12 controls. Lipid profile, free fatty acids, glucose, and insulin were measured. Lipid content in liver and visceral fat were assessed. Isolated VLDL (d<1.006g/ml) was characterized by its chemical composition and size by HPLC. The respective hepatic expression of SREBP-1c and PPAR-α was determined (Western blot).
  
  
  RESULTS
  As expected, SRD had elevated triglycerides (TG), free fatty acids and insulin levels, and decreased HDL-cholesterol (p<0.05), together with augmented hepatic and visceral fat (p<0.05). SRD showed higher VLDL total mass - with increased TG content - and predominance of large VLDL (p<0.05). SRD showed an increase in SREBP-1c (precursor and mature forms) and decreased PPAR-α expression (p<0.045). SREBP-1c forms were positively associated with VLDL total mass (p<0.04), VLDL-TG% (p<0.019), and large VLDL% (p<0.002). On the other hand, PPAR-α correlated negatively with VLDL total mass (p=0.05), VLDL-TG% (p=0.005), and large VLDL% (p=0.002).
  
  
  CONCLUSIONS
  Insulin-resistance, by coordinated activation of SREBP-1c and reduction of PPAR-α, could promote the secretion of larger and TG over-enriched VLDL particles, with greater atherogenic capacity.
authors: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina. Electronic address: dmlucero@ffyb.uba.ar.
authors: Diego
authors: D
authors: Lucero
authors: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.
authors: Verónica
authors: V
authors: Miksztowicz
authors: Oral and General Biochemistry Department, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors: Vanesa
authors: V
authors: Macri
authors: Bioanalytics, Department of Biology, Biochemistry and Pharmacy, National Southern University, Bahía Blanca, Buenos Aires, Argentina.
authors: Gustavo H
authors: GH
authors: López
authors: Oral and General Biochemistry Department, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors: Silvia
authors: S
authors: Friedman
authors: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.
authors: Gabriela
authors: G
authors: Berg
authors: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.
authors: Valeria
authors: V
authors: Zago
authors: Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.
authors: Laura
authors: L
authors: Schreier
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000378:metabolism; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008079:Lipoproteins, VLDL; D047493:PPAR alpha; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides
keywords: Dieta rica en sacarosa; Insulin-resistance; Insulinorresistencia; Large very low density lipoprotein; Lipoproteínas de muy baja densidad grandes; Peroxisome proliferator-activated receptor-α; Proteína ligadora de elementos reguladores de esteroles-1c; Receptores activados por factores de proliferación peroxisomal-α; Sterol regulatory element binding protein 1c; Sucrose rich diet