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Journal of Lipid Research, Vol. 46, 1823-1832, September 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

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

Armando R. Tovar^*, Ivan Torre-Villalvazo^*, Melissa Ochoa^*, Ana L. Elías^*, Victor Ortíz^*, Carlos A. Aguilar-Salinas and Nimbe Torres^1,*

^* Departments of Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," México, D.F., México
Endocrinologia y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," México, D.F., México

Published, JLR Papers in Press, July 1, 2005. DOI 10.1194/jlr.M500067-JLR200

¹ To whom correspondence should be addressed. e-mail: nimbet{at}quetzal.innsz.mx

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity attributable in part to an accelerated lipogenesis. There is evidence that a soy protein diet prevents the overexpression of hepatic sterol-regulatory element binding protein-1 (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 and triglyceride levels, as well as VLDL-triglyceride and LDL-cholesterol, were significantly lower in rats fed soy protein than in rats fed a casein diet for 160 days. The reduction in hepatic cholesterol was associated with a low expression of liver X receptor- and its target genes, 7- hydroxylase and ABCA1. Soy protein also decreased the expression of SREBP-1 and several of its target genes, FAS, stearoyl-CoA desaturase-1, and 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 helps prevent the development of hepatic lipotoxicity.

Supplementary key words steatosis • liver • liver X receptor- • sterol-regulatory element binding protein-1

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