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, beta-hydroxy-beta-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.