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Nutrient-Gene Interactions

A Soy Protein Diet Alters Hepatic Lipid Metabolism Gene Expression and Reduces Serum Lipids and Renal Fibrogenic Cytokines in Rats with Chronic Nephrotic Syndrome¹

Armando R. Tovar^*, Fernanda Murguía^*, Cristino Cruz, Rogelio Hernández-Pando^**, Carlos A. Aguilar-Salinas, José Pedraza-Chaverri, Ricardo Correa-Rotter and Nimbe Torres^*2

Departments of ^* Fisiología de la Nutrición, Nefrología y Metabolismo Mineral, ^** Patología Experimental, Diabetes y Metabolismo de Lípidos, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," y Department of Biología, Facultad de Química, Universidad Nacional Autónoma de México, México, D.F, México

²To whom correspondence should be addressed. E-mail: nimbet{at}quetzal.innsz.mx.

Nephrotic syndrome (NS) is characterized by the presence of proteinuria and hyperlipidemia. However, ingestion of soy protein has a hypolipidemic effect. The present study was designed to determine whether the ingestion of a 20% soy protein diet regulates the expression of hepatic sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), malic enzyme, ß-hydroxy-ß-methylglutaryl-CoA (HMG-CoA) reductase (r) and synthase (s), and LDL receptor (r), and to assess whether soy protein improves lipid and renal abnormalities in rats with chronic NS. Male Wistar rats were injected with vehicle or with puromycin aminonucleoside to induce NS and were fed either 20% casein or soy protein diets for 64 d. NS rats fed 20% soy protein had improved creatinine clearance and reduced proteinuria, hypercholesterolemia, hypertriglyceridemia, as well as VLDL-triglycerides and LDL cholesterol compared with NS rats fed the 20% casein diet. In addition, the soy protein diet decreased the incidence of glomerular sclerosis, and proinflammatory cytokines in kidney. Ingestion of the soy protein diet by control rats reduced the gene expression of SREBP-1, malic enzyme, FAS and increased HMG-CoAr, HMG-CoAs and LDLr. However, NS rats fed either casein or soy protein diets had low insulin concentrations with reductions in SREBP-1, FAS and malic enzyme expression compared with control rats fed the casein diet. NS rats fed the soy diet also had lower HMG-CoAr and LDLr mRNA levels than NS rats fed casein. In conclusion, the beneficial effects of soy protein on lipid metabolism are modulated in part by SREBP-1. However, in NS rats, the benefit may be through a direct effect of this protein on kidney rather than mediated by changes in expression of hepatic lipid metabolism genes.

KEY WORDS: • nephrotic syndrome • lipid metabolism • rats • soy protein • sterol regulatory element binding protein-1

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