Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats.
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-alpha and its target genes, 7-alpha hydroxylase and ABCA1. Soy protein also decreased the expression of SREBP-1 and several of its target genes, FAS, stearoyl-CoA desaturase-1, and delta5 and delta6 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.
Department of Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, DF, México.
Armando R
AR
Tovar
Ivan
I
Torre-Villalvazo
Melissa
M
Ochoa
Ana L
AL
Elías
Victor
V
Ortíz
Carlos A
CA
Aguilar-Salinas
Nimbe
N
Torres
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002364:Caseins / Q000008:administration & dosage; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D008078:Cholesterol, LDL / Q000032:analysis / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004032:Diet; D005234:Fatty Liver / Q000209:etiology* / Q000517:prevention & control*; D015870:Gene Expression; D006946:Hyperinsulinism / Q000150:complications*; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000032:analysis / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D009765:Obesity / Q000150:complications*; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D030262:Soybean Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000032:analysis / Q000097:blood
D022762:CCAAT-Enhancer-Binding Proteins; D002364:Caseins; D008078:Cholesterol, LDL; D004268:DNA-Binding Proteins; D008079:Lipoproteins, VLDL; D000071518:Liver X Receptors; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D030262:Soybean Proteins; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002784:Cholesterol