title: Dietary soy protein isolate attenuates metabolic syndrome in rats via effects on PPAR, LXR, and SREBP signaling.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA. ronismartinj@uams.edu <ronismartinj@uams.edu>
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Jamie
authors.initials: J
authors.lastname: Badeaux
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
mesh_terms: 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
chemical_list: 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