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Overproduction of altered VLDL in an insulin-resistance rat model: Influence of SREBP-1c and PPAR-α.
Clin Investig Arterioscler 2015 Jul-Aug; 27(4):167-74CI

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+Show Affiliations

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.Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.Oral and General Biochemistry Department, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.Bioanalytics, Department of Biology, Biochemistry and Pharmacy, National Southern University, Bahía Blanca, Buenos Aires, Argentina.Oral and General Biochemistry Department, Faculty of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25796423

Citation

Lucero, Diego, et al. "Overproduction of Altered VLDL in an Insulin-resistance Rat Model: Influence of SREBP-1c and PPAR-α." Clinica E Investigacion En Arteriosclerosis : Publicacion Oficial De La Sociedad Espanola De Arteriosclerosis, vol. 27, no. 4, 2015, pp. 167-74.
Lucero D, Miksztowicz V, Macri V, et al. Overproduction of altered VLDL in an insulin-resistance rat model: Influence of SREBP-1c and PPAR-α. Clin Investig Arterioscler. 2015;27(4):167-74.
Lucero, D., Miksztowicz, V., Macri, V., López, G. H., Friedman, S., Berg, G., ... Schreier, L. (2015). Overproduction of altered VLDL in an insulin-resistance rat model: Influence of SREBP-1c and PPAR-α. Clinica E Investigacion En Arteriosclerosis : Publicacion Oficial De La Sociedad Espanola De Arteriosclerosis, 27(4), pp. 167-74. doi:10.1016/j.arteri.2014.11.002.
Lucero D, et al. Overproduction of Altered VLDL in an Insulin-resistance Rat Model: Influence of SREBP-1c and PPAR-α. Clin Investig Arterioscler. 2015;27(4):167-74. PubMed PMID: 25796423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overproduction of altered VLDL in an insulin-resistance rat model: Influence of SREBP-1c and PPAR-α. AU - Lucero,Diego, AU - Miksztowicz,Verónica, AU - Macri,Vanesa, AU - López,Gustavo H, AU - Friedman,Silvia, AU - Berg,Gabriela, AU - Zago,Valeria, AU - Schreier,Laura, Y1 - 2015/03/18/ PY - 2014/10/15/received PY - 2014/11/06/revised PY - 2014/11/07/accepted PY - 2015/3/23/entrez PY - 2015/3/23/pubmed PY - 2016/12/15/medline KW - Dieta rica en sacarosa KW - Insulin-resistance KW - Insulinorresistencia KW - Large very low density lipoprotein KW - Lipoproteínas de muy baja densidad grandes KW - Peroxisome proliferator-activated receptor-α KW - Proteína ligadora de elementos reguladores de esteroles-1c KW - Receptores activados por factores de proliferación peroxisomal-α KW - Sterol regulatory element binding protein 1c KW - Sucrose rich diet SP - 167 EP - 74 JF - Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis JO - Clin Investig Arterioscler VL - 27 IS - 4 N2 - 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. SN - 1578-1879 UR - https://www.unboundmedicine.com/medline/citation/25796423/Overproduction_of_altered_VLDL_in_an_insulin_resistance_rat_model:_Influence_of_SREBP_1c_and_PPAR_α_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0214-9168(14)00170-3 DB - PRIME DP - Unbound Medicine ER -