Dietary soy protein isolate attenuates metabolic syndrome in rats via effects on PPAR, LXR, and SREBP signaling.
To determine the effects of feeding soy or isoflavones on lipid homeostasis in early development, weanling rats were fed AIN-93G diets made with casein, soy protein isolate (SPI+), isoflavone-reduced SPI+ (SPI-), or casein supplemented with genistein or daidzein for 14 d. PPARalpha-regulated genes and proteins involved in fatty acid degradation were upregulated by SPI+ (P < 0.05) accompanied by increased promoter binding and expression of PPARalpha mRNA (P < 0.05). Feeding SPI- or pure isoflavones did not alter PPARalpha-regulated pathways. SPI+ feeding had similar effects on PPARgamma signaling. SPI+, SPI-, and casein plus isoflavones all increased liver X-receptor (LXR)alpha-regulated genes and enzymes involved in cholesterol homeostasis. Feeding SPI+ increased promoter binding of LXRalpha, expression of the transcription factor mRNA, and protein (P < 0.05). In a second experiment, male Sprague-Dawley rats were fed casein diets from postnatal d (PND) 24 to PND64 or were fed high-fat Western diets containing 5 g x kg(-1) cholesterol made with either casein or SPI+. Insulin resistance, steatosis, and hypercholesterolemia in the Western diet-fed rats were partially prevented by SPI+ (P < 0.05). Nuclear sterol receptor element binding protein (SREBP)-1c protein and mRNA and protein expression of enzymes involved in fatty acid synthesis were increased by feeding Western diets containing casein but not SPI+ (P < 0.05). These data suggest that activation of PPAR and LXR signaling and inhibition of SREBP-1c signaling may contribute to insulin sensitization and improved lipid homeostasis in SPI+-fed rats after consumption of diets high in fat and cholesterol.
Ronis
Martin J
MJ
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA. ronismartinj@uams.edu <ronismartinj@uams.edu>
Chen
Ying
Y
Badeaux
Jamie
J
Badger
Thomas M
TM
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats; D005234:Fatty Liver / Q000517:prevention & control; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000517:prevention & control; D007333:Insulin Resistance; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D000071518:Liver X Receptors; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D030262:Soybean Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
D000924:Anticholesteremic Agents; D002364:Caseins; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D007529:Isoflavones; D000071518:Liver X Receptors; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D030262:Soybean Proteins; D051780:Sterol Regulatory Element Binding Protein 1; C004742:daidzein; D002784:Cholesterol; D019833:Genistein