Showing papers by "Martin J. J. Ronis published in 2009"
TL;DR: In this paper, weanling rats were fed AIN-93G diets made with casein, soy protein isolate (SPI+), isoflavone-reduced SPI+, or casein supplemented with genistein or daidzein for 14 d.
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.
133 citations
TL;DR: It is concluded that inhibitory cross‐talk between EtOH and E2 in osteoblasts on ERs, p53/p21, and cell senescence provides a pathophysiologic mechanism underlying bone loss and the protective effects of estrogens in alcohol‐exposed females.
Abstract: Epidemiological and animal studies have suggested that chronic alcohol consumption is a major risk factor for osteoporosis. Using bone from cycling female rats infused chronically with ethanol (EtOH) in vivo and osteoblastic cells in vitro, we found that EtOH significantly increased estrogen receptor α (ERα) and β (ERβ) mRNA and ERα protein levels. Treatment with 17β-estradiol (E2) in vivo and in vitro interfered with these effects of EtOH on bone and osteoblastic cells. ERα agonist propylpyrazoletriol (PPT) and ERβ agonist diarylpropionitrile (DPN) attenuated EtOH-induced ERα and ERβ gene overexpression, respectively. Similar to the ER antagonist ICI 182780, EtOH blocked nuclear translocation of ERα-ECFP in the presence of E2 in UMR-106 osteoblastic cells. EtOH also downregulated ERE-luc reporter activity. On the other hand, EtOH by itself upregulated some common ERα- and ERβ-mediated genes apparently by an ER-independent pathway. EtOH also transactivated the luciferase activity of the p21 promoter region independent of additional exogenous ERα, activated p21 and p53, and stimulated senescence-associated β-galactosidase activity in rat stromal osteoblasts. E2 treatment attenuated these EtOH actions. We conclude that inhibitory cross-talk between EtOH and E2 in osteoblasts on ERs, p53/p21, and cell senescence provides a pathophysiologic mechanism underlying bone loss and the protective effects of estrogens in alcohol-exposed females.
67 citations
TL;DR: It is demonstrated that neonatal piglets fed with soy- based formula and cow milk-based formula for 21 or 35 d had greater bone mineral density and content than breast-fed piglets (BF) and SF piglets had the highest bone volume over tissue volume, suggesting that SF- fed piglets may have the best quality bone.
Abstract: Relatively few studies have examined the effects of formula feeding relative to breast-feeding on bone in the neonate. Using peripheral quantitative CT scan and histomorphometric analysis, we demonstrated that neonatal piglets fed with soy-based formula (SF) and cow milk-based formula (MF) for 21 or 35 d had greater bone mineral density and content than breast-fed piglets (BF) (P < 0.05). Osteoblast numbers and bone formation rate at postnatal d 35 were greater in SF compared with other groups (P < 0.05), whereas osteoclast numbers were lower in both MF and SF groups than in the BF group (P < 0.05). Osteoblastogenesis was greater in ex vivo bone marrow cell cultures from SF than in MF or BF piglets (P < 0.05). Bone formation markers in serum were greater, whereas bone resorption markers were lower in the MF- and SF-fed groups than in the BF group (P < 0.05). Bone morphogenic protein (BMP) 2 and alkaline phosphatase mRNAs were upregulated in the MF and SF groups compared with the BF group (P < 0.05), whereas receptor activator of NF-kappaB ligand was downregulated (P < 0.05). Extracellular signal-regulated kinase, p38, Smad1/5/8 phosphorylation, and runt-related transcription factor 2 expression were greater in bone from the MF and SF groups compared with the BF group (P < 0.05). In vitro studies showed that 2.5% serum from SF- or MF-fed piglets was able to stimulate osteoblast differentiation but not in the presence of the BMP blocker noggin. Therefore, formula feeding promoted bone growth compared with BF. SF piglets had the highest bone volume over tissue volume. This suggests that SF-fed piglets may have the best quality bone. The anabolic effects of SF on bone appear to be mediated through enhanced BMP signaling.
38 citations
TL;DR: The different hepatic gene signatures produced by SPI feeding compared with E(2) and the lack of increase in uterine wet weight in rats fed with SPI suggest that SPI is not estrogenic in these tissues.
Abstract: Although soy foods have been recognized as an excellent source of protein, there have been recent concerns regarding potential adverse effects of isoflavone phytochemicals found in soy products, which are known to bind and activate estrogen receptors. Here, we used global hepatic gene expression profiles in ovariectomized female Sprague-Dawley rats treated with 17beta-estradiol (E(2)) or fed with soy protein isolate (SPI) as a means of estimating potential estrogenicity of SPI. Female Sprague-Dawley rats were fed AIN-93G diets containing casein (CAS) or SPI starting at postnatal day (PND) 30. Rats were ovariectomized on PND 50 and infused with E(2) or vehicle in osmotic pumps for 14 d. Microarray analysis was performed on liver using Affymetrix GeneChip Rat 230 2.0. Serum E(2) levels were within normal ranges for the rat and SPI feeding did not increase uterine wet weight in the absence or presence of E(2). SPI feeding altered (P or=+/-1.5-fold) the expression of 82 genes, while E(2) treatment altered 892 genes. Moreover, only 4% of E(2)-affected genes were also modulated by SPI, including some whose expression was reversed by SPI feeding. The interaction between E(2) and SPI uniquely modulated the expression profile of 225 genes including the reduction of those involved in fatty acid biosynthesis or glucocorticoid signaling and an induction of those involved in cholesterol metabolism. The different hepatic gene signatures produced by SPI feeding compared with E(2) and the lack of increase in uterine wet weight in rats fed with SPI suggest that SPI is not estrogenic in these tissues.
29 citations
TL;DR: The data suggest that although E2 status does not effect soy-mediated AhR degradation, it modulates the effects of soy on many genes, including CYP1A1.
8 citations