Over-production of altered VLDL in an insulin-resistance rat model: influence of SREBP-1c and PPAR-α

LUCERO D; MIKSZTOWICZ V; MACRI EV; LOPEZ GH; FRIEDMAN S; BERG G; ZAGO V; SCHREIER L

Clínica e Investigación en Areteriosclerosis

Elsevier

Año: 2015 vol. 27 p. 167 - 174

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 peroxisomeproliferator-activated receptor- (PPAR-), with the features of composition and size of VLDL in an insulin-resistance rat model induced by a sucrose rich diet (SRD). Methods: A study was conducted on 12 male Wistar rats (180 g) receiving SRD (12 weeks) and 12 controls. Lipid profile, free fatty acids, glucose, and insulin were measured. Lipid content in liver and visceral fat was assessed. Isolated VLDL (d < 1.006 g/ml) was characterized by its chemical composition and size by HPLC. The respective hepatic expression of SREBP-1c and PPAR- 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 predominanceof large VLDL (p < 0.05). SRD showed an increase in SREBP-1c (precursor and mature forms) and decreased PPAR- 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- correlated negatively with VLDL total mass (p = 0.05), VLDL-TG% (p = 0.005), and large VLDL% (p = 0.002).