J. Lipid Res.
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A more recent version of this article appeared on September 1, 2005

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J. Lipid Res., doi:10.1194/jlr.M500067-JLR200
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Submitted on February 18, 2005
Revised on June 14, 2005
Accepted on June 24, 2005

Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats

Armando R. Tovar, Ivan Torre-Villalvazo, Melissa Ochoa, Ana L. Elias, Victor Ortiz, Carlos A. Aguilar-Salinas, and Nimbe Torres

Physiology of Nutrition, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico, DF 14000

Corresponding Author: nimbet{at}quetzal.innsz.mx

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity due in part to an accelerated lipogenesis. There is evidence that soy protein diet prevents the overexpression of hepatic SREBP-1 decreasing lipid accumulation. Therefore the aim of the present work was to study whether a soy protein diet may prevent the development of fatty liver through the regulation of transcription factors involved in lipid metabolism in hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats. Serum and hepatic cholesterol (C) and triglyceride (T) levels, as well as VLDL-T and LDL-C were significantly lower in rats fed soy protein than rats a fed casein diet for 160 days. The reduction in hepatic cholesterol was associated with a low expression of LXR-a and its target genes: CYP7A1 and ABCA1. Soy protein also decreased the expression of SREBP-1 as well as several of its target genes FAS, SCD-1, 5 and 6 desaturases, decreasing lipogenesis even in the presence of hyperinsulinemia. Reduction in SREBP-1 was not associated with the presence of soy isoflavones. Finally, soy protein reduced SREBP-1 expression in adipocytes preventing hypertrophy, which also contribute to prevent the development of hepatic lipotoxicity.


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