Showing papers by "Thomas M. Badger published in 2010"
TL;DR: This review attempts to summarize major non-isoflavone phytochemicals in soy, as well as their bioavailability and health effects.
Abstract: Epidemiological and clinical studies have linked consumption of soy foods with low incidences of a number of chronic diseases, such as cardiovascular diseases, cancer, and osteoporosis. Over the past decades, enormous research efforts have been made to identify bioactive components in soy. Isoflavones and soy protein have been suggested as the major bioactive components in soy and have received considerable attention. However, there are hundreds of phytochemical components in soybeans and soy-based foods. In recent years, accumulating evidence has suggested that the isoflavones or soy proteins stripped of phytochemicals only reflect certain aspects of health effects associated with soy consumption. Other phytochemicals, either alone or in combination with isoflavones or soy protein, may be involved in the health effects of soy. This review attempts to summarize major non-isoflavone phytochemicals in soy, as well as their bioavailability and health effects. In addition, a brief discussion of components formed during food processing is also included.
129 citations
TL;DR: Results indicate stimulation of molecular events leading to osteoblast differentiation triggered by P38 MAP kinase (MAPK)/β‐catenin canonical Wnt signaling results in significant increases in bone growth in young rats consuming BB‐supplemented diets.
Abstract: Diet and nutritional status are critical factors that influences bone development. In this report we demonstrate that a mixture of phenolic acids found in the serum of young rats fed blueberries (BB) significantly stimulated osteoblast differentiation, resulting in significantly increased bone mass. Greater bone formation in BB diet-fed animals was associated with increases in osteoblast progenitors and osteoblast differentiation and reduced osteoclastogenesis. Blockade of p38 phosphorylation eliminated effects of BB on activation of Wnt signaling in preosteoblasts. Knocking down β-catenin expression also blocked the ability of serum from BB diet-fed rats to stimulate osteoblast differentiation in vitro. Based on our in vivo and in vitro data, we propose that the underlying mechanisms of these powerful bone-promoting effects occur through β-catenin activation and the nuclear accumulation and transactivation of TCF/LEF gene transcription in bone and in osteoblasts. These results indicate stimulation of molecular events leading to osteoblast differentiation triggered by P38 MAP kinase (MAPK)/β-catenin canonical Wnt signaling results in significant increases in bone growth in young rats consuming BB-supplemented diets. Liquid chromatography/mass spectrometry (LC/MS) characterization of the serum after BB feeding revealed a mixture of simple phenolic acids that may provide a basis for developing a new treatment to increase peak bone mass and delay degenerative bone disorders such as osteoporosis.
126 citations
TL;DR: The results strongly suggest that gestational exposure to maternal obesity programs multiple aspects of energy-balance regulation in the offspring.
Abstract: Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult life. Male offspring from OW dams gain greater body weight and fat mass and develop insulin resistance when fed high-fat diets (45% fat). In this report, we identify molecular targets of maternal OW-induced programming at postnatal d 21 before challenge with the high-fat diet. We conducted global transcriptome profiling, gene/protein expression analyses, and characterization of downstream signaling of insulin and adiponectin pathways in conjunction with endocrine and biochemical characterization. Offspring born to OW dams displayed increased serum insulin, leptin, and resistin levels (P < 0.05) at postnatal d 21 preceding changes in body composition. A lipogenic transcriptome signature in the liver, before development of obesity, was evident in OW-dam offspring. A coordinated locus of 20 sterol regulatory element-binding protein-1-regulated target genes was induced by maternal OW. Increased nuclear levels of sterol regulatory element-binding protein-1 and recruitment to the fatty acid synthase promoter were confirmed via ELISA and chromatin immunoprecipitation analyses, respectively. Higher fatty acid synthase and acetyl coenzyme A carboxylase protein and pAKT (Thr(308)) and phospho-insulin receptor-beta were confirmed via immunoblotting. Maternal OW also attenuated AMP kinase/peroxisome proliferator-activated receptor-alpha signaling in the offspring liver, including transcriptional down-regulation of several peroxisome proliferator-activated receptor-alpha-regulated genes. Hepatic mRNA and circulating fibroblast growth factor-21 levels were significantly lower in OW-dam offspring. Furthermore, serum levels of high-molecular-weight adiponectin (P < 0.05) were decreased in OW-dam offspring. Phosphorylation of hepatic AMP-kinase (Thr(172)) was significantly decreased in OW-dam offspring, along with lower AdipoR1 mRNA. Our results strongly suggest that gestational exposure to maternal obesity programs multiple aspects of energy-balance regulation in the offspring.
114 citations
TL;DR: The observations strongly suggest that increased NEFA in serum from rats made obese by HFD-feeding impaired bone formation due to stimulation of bone marrow adipogenesis and may result in impaired attainment of peak bone mass and therefore increase the prevalence of osteoporosis later on in life.
Abstract: Background: It is well established that excessive consumption of a high fat diet (HFD) results in obesity; however, the consequences of obesity on postnatal skeletal development have not been well studied. Methodology and Principal Findings: Total enteral nutrition (TEN) was used to feed postnatal day 27 male rats intragastrically with a high 45% fat diet (HFD) for four weeks to induce obesity. Fat mass was increased compared to rats fed TEN diets containing 25% fat (medium fat diet, MFD) or a chow diet (low fat diet, LFD) fed ad libitum with matched body weight gains. Serum leptin and total non-esterified fatty acids (NEFA) were elevated in HFD rats, which also had reduced bone mass compared to LFD-fed animals. This was accompanied by decreases in bone formation, but increases in the bone resorption. Bone marrow adiposity and expression of adipogenic genes, PPARc and aP2 were increased, whereas osteoblastogenic markers osteocalcin and Runx2 were decreased, in bone in HFD rats compared to LFD controls. The diversion of stromal cell differentiation in response to HFD stemmed from down-regulation of the key canonical Wnt signaling molecule b-catenin protein and reciprocal up-regulation of nuclear PPARc expression in bone. In a set of in vitro studies using pluripotent ST2 bone marrow mesenchymal stromal cells treated with serum from rats on the different diets or using the free fatty acid composition of NEFA quantified in rat serum from HFD-fed animals by GC-MS, we were able to recapitulate our in vivo findings. Conclusions/Significance: These observations strongly suggest that increased NEFA in serum from rats made obese by HFD-feeding impaired bone formation due to stimulation of bone marrow adipogenesis. These effects of obesity on bone in early life may result in impaired attainment of peak bone mass and therefore increase the prevalence of osteoporosis later on in life.
110 citations
TL;DR: Real‐time array analysis of total RNA isolated from bone tissue revealed that the majority of Wnt signaling components were downregulated by chronic ethanol infusion, consistent with the hypothesis that ethanol inhibits bone formation through stimulation of oxidative stress to suppress Wnt signalling.
Abstract: The mechanisms by which chronic ethanol intake induces bone loss remain unclear. In females, the skeletal response to ethanol varies depending on physiologic status (e.g., cycling, pregnancy, or lactation). Ethanol-induced oxidative stress appears to be a key event leading to skeletal toxicity. In this study, ethanol-containing liquid diets were fed to postlactational female Sprague-Dawley rats intragastrically for 4 weeks beginning at weaning. Ethanol consumption decreased bone mineral density (BMD) compared with control animals during this period of bone rebuilding following the end of lactation. Coadministration of the antioxidant N-acetylcysteine (NAC) was able to block bone loss and downregulation of the bone-formation markers alkaline phosphatase and osteocalcin in serum and gene expression in bone. Real-time array analysis of total RNA isolated from bone tissue revealed that the majority of Wnt signaling components were downregulated by chronic ethanol infusion. Real-time PCR confirmed downregulated gene expression in a subset of the Wnt signaling components by ethanol. However, the Wnt antagonist DKK1 was upregulated by ethanol. The key canonical Wnt signaling molecule β-catenin protein expression was inhibited, while glycogen synthase kinase-3-β was dephosphorylated by ethanol in bone and preosteoblastic cells. These actions of ethanol were blocked by NAC. Ethanol treatment inactivated TCF/LEF gene transcription, eliminated β-catenin nuclear translocation in osteoblasts, and reciprocally suppressed osteoblastogenesis and enhanced adipogenesis. These effects of ethanol on lineage commitment of mesenchymal stem cells were eliminated by NAC pretreatment. These observations are consistent with the hypothesis that ethanol inhibits bone formation through stimulation of oxidative stress to suppress Wnt signaling. © 2010 American Society for Bone and Mineral Research.
101 citations
TL;DR: A protective effectiveness of BB against atherosclerosis in this apoE(-/-) mouse model is suggested and the potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation and enhancement of antioxidant defense.
Abstract: Protective effects of blueberries (BB) against atherosclerosis and potential underlying mechanisms in reducing oxidative stress were examined in apoE-deficient (apoE(-/-)) mice. ApoE(-/-) mice were fed an AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried whole BB for 20 wk. The mean lesion area for apoE(-/-) mice fed BB was reduced by 39% (P < 0.001) in the aorta sinus and 58% (P < 0.001) in the descending aorta compared with CD-fed mice. These atheroprotective effects were independent of the serum lipid profile or total antioxidant capacity (as measured by oxygen radical absorbance capacity). The concentration of a biomarker of lipid peroxidation, F(2)-isoprostane, was lower in liver of BB-fed mice (P < 0.05). Genes analyzed by RT-PCR array showed that 4 major antioxidant enzymes in aorta [superoxide dismutase (SOD) 1, SOD2, glutathione reductase (GSR), and thioredoxin reductase 1] were upregulated in BB-fed mice. Enzyme activities of SOD and GSR were greater (P < 0.05) in liver and/or serum of BB-fed mice than those of CD-fed mice. In addition, serum paraoxonase 1 activity in serum of BB-fed mice was also greater than that of CD-fed mice (P < 0.05) at the end of the study. These results suggest a protective effectiveness of BB against atherosclerosis in this apoE(-/-) mouse model. The potential mechanisms may involve reduction in oxidative stress by both inhibition of lipid peroxidation and enhancement of antioxidant defense.
98 citations
TL;DR: The intent of the workshop was to address the quality of soy studies, not the efficacy or safety of soy, and the resulting guidance is specific to soy clinical research and does not address nonsoy-related factors that should also be considered in designing and reporting clinical studies.
Abstract: The NIH sponsored a scientific workshop, "Soy Protein/Isoflavone Research: Challenges in Designing and Evaluating Intervention Studies," July 28-29, 2009. The workshop goal was to provide guidance for the next generation of soy protein/isoflavone human research. Session topics included population exposure to soy; the variability of the human response to soy; product composition; methods, tools, and resources available to estimate exposure and protocol adherence; and analytical methods to assess soy in foods and supplements and analytes in biologic fluids and other tissues. The intent of the workshop was to address the quality of soy studies, not the efficacy or safety of soy. Prior NIH workshops and an evidence-based review questioned the quality of data from human soy studies. If clinical studies are pursued, investigators need to ensure that the experimental designs are optimal and the studies properly executed. The workshop participants identified methodological issues that may confound study results and interpretation. Scientifically sound and useful options for dealing with these issues were discussed. The resulting guidance is presented in this document with a brief rationale. The guidance is specific to soy clinical research and does not address nonsoy-related factors that should also be considered in designing and reporting clinical studies. This guidance may be used by investigators, journal editors, study sponsors, and protocol reviewers for a variety of purposes, including designing and implementing trials, reporting results, and interpreting published epidemiological and clinical studies.
65 citations
TL;DR: Data suggest that a significant proportion of hepatic injury after ethanol exposure is independent of alcohol metabolism, and CYP2E1 may be linked in part to triglyceride accumulation, to induction of TNF-alpha, and to chemokine production.
64 citations
TL;DR: The data do not support major diet-related differences in reproductive organ size as measured by ultrasound in infants at age 4 months, although there is some evidence that ovarian development may be advanced in MF-fed infants and that testicular development might be slower in both MF and SF infants as compared with BF.
59 citations
TL;DR: It is shown that aged‐related deficits in direct bone formation can be restored to young mice by treatment with TNF blockers and that the cyclin‐dependent kinase inhibitor p21 is a candidate for mediation of the osteoinhibitory effects of TNF.
Abstract: Skeletal changes accompanying aging are associated with both increased risk of fractures and impaired fracture healing, which, in turn, is due to compromised bone regeneration potential. These changes are associated with increased serum levels of selected proinflammatory cytokines, e.g., tumor necrosis factor α (TNF-α). We have used a unique model of bone regeneration to demonstrate (1) that aged-related deficits in direct bone formation can be restored to young mice by treatment with TNF blockers and (2) that the cyclin-dependent kinase inhibitor p21 is a candidate for mediation of the osteoinhibitory effects of TNF. It has been hypothesized recently that TNF antagonists may represent novel anabolic agents, and we believe that the data presented here represent a successful test of this hypothesis. © 2010 American Society for Bone and Mineral Research
55 citations
TL;DR: The development of brain electrical activity during infancy differs between those who are breastfed compared with those fed either milk or soy formula, but is generally similar for formula-fed groups.
TL;DR: It is suggested that C/F and interactions with excessive caloric intake per se may regulate body composition and play important roles in the development of obesity and metabolic syndrome.
Abstract: Although obesity is often associated with high-fat diets, it can develop from a variety of meal patterns. Excessive intake of simple carbohydrates is one consistent eating behavior leading to obesity. However, the impact of overconsumption of diets with high carbohydrate to fat ratios (C/F) on body composition and global adipose tissue gene expression remains unclear. We used total enteral nutrition to evaluate the effects of caloric intake and C/F on body weight gain and development of obesity. Female Sprague Dawley rats were fed diets with either low C/F or high C/F (HC) (reflecting a 19.5-fold increase in C/F) at two levels of caloric intake: 187 or 220 kcal/kg3/4 · d (15% excess) for 4 wk. At the end of the study period, rats fed HC diets had about 20% higher body weight at either caloric intake compared with rats fed low C/F diets (P < 0.05). Body composition (assessed by nuclear magnetic resonance, computerized tomography, and adipose tissue weights) revealed higher percent fat mass (P < 0.05) in HC...
TL;DR: QMR provides precise and accurate measures of FM, FFM and TBW in piglets weighing up to 50 kg and suggests that QMR should provide the opportunity to acquire valuable body composition data in longitudinal studies in children, which is not possible or practical with other commercially available instrumentation.
Abstract: QMR: validation of an infant and children body composition instrument using piglets against chemical analysis
TL;DR: Comparisons of behavioral development and cortical responses to speech sounds in infants fed either breast milk or formula and ERP measures revealed diet- and gender-specific emphases that may reflect differences in developmental trajectories of brain–behavior relationships.
Abstract: Controversy exists about the safety of soy formula, with the main concern relating to potential estrogenic effects of soy protein. Since estrogens influence early brain development, we compared behavioral development and cortical responses (event-related potentials; ERPs) to speech sounds in infants fed either breast milk or formula (milk- or soy-based). Across-groups ERP measures were generally similar and behavioral measures were within normal ranges, suggesting no important influences of soy formula on behavioral development and brain function during the study period. Analyses relating ERP and behavioral measures revealed diet- and gender-specific emphases that may reflect differences in developmental trajectories of brain-behavior relationships.
TL;DR: This article showed that excessive intake of a high-fat diet in young rats results in increases in ectopic fat deposition and hyperinsulinemia, and suggest age-related differences in the role of adiponectin in pathological responses associated with obesity.
Abstract: Serum adiponectin has been reported to inversely correlate with the degree of adiposity in children. However, the relative contribution of adiponectin-dependent signaling to the development of metabolic syndrome in childhood obesity is unclear. We overfed prepubertal, male Sprague-Dawley rats a high-fat diet via total enteral nutrition. Excessive caloric intake led to obesity, increased body weight and fat mass; dyslipidemia; ectopic fat deposition; and hyperinsulinemia (P<.05). Expression of fatty acid transporter FAT/CD36 was elevated in both liver and skeletal muscle (P<.05). Hepatic Akt phosphorylation was elevated (P<.05) and FoxO1 protein in hepatic nuclear extracts was reduced (P<.05) in the face of hyperinsulinemia, whereas no increase in Akt phosphorylation or decrease in nuclear FoxO1 was observed in skeletal muscle. Overfeeding increased serum adiponectin concentration from 24.6±1.9 μg/ml to 46.3±5.9 μg/ml (P<.004), and positively correlated with increased adipose tissue mass. The expression of the inflammatory cytokine tumor necrosis factor α in the adipose tissue was unchanged. Adiponectin-mediated adenosine monophosphate (AMP) kinase phosphorylation, peroxisome proliferator-activator receptor-α expression and the expression of genes involved in fatty acid oxidation were elevated in both liver and muscle (P<.05). These data (1) demonstrate that excessive intake of a high-fat diet in young rats results in \"adiponectin-independent\" increases in ectopic fat deposition and hyperinsulinemia, (2) suggest that fatty acid transport is a major mechanism underlying ectopic fat deposition, (3) demonstrate tissue-specific differences in the response of Akt-FoxO signaling to hyperinsulinemia following the development of pediatric obesity and (4) suggest age-related differences in the role of adiponectin in pathological responses associated with obesity.
TL;DR: In the present study, the effects of a shiitake diet were evaluated on the basis of identification and quantification of individual polar lipid components in rat serum using liquid chromatography-mass spectrometry/mass Spectrometry and the concentrations of 27 polar lipids inRat serum were determined.
Abstract: Consumption of a shiitake mushroom diet has been reported to have effects on serum phospholipids. However, much less is known about the effect on serum polar lipids including lysophospholipids and free fatty acids. In the present study, the effects of a shiitake diet were evaluated on the basis of identification and quantification of individual polar lipid components in rat serum using liquid chromatography−mass spectrometry/mass spectrometry. By comparison with standards and published data, 50 lysophospholipids and 32 free fatty acids were identified, and the concentrations of 27 polar lipids in rat serum were determined. Shiitake diets decreased the levels of all individual polar lipid components in the serum of male rat. The total level of serum polar lipids in males fed 4% shiitake diets (1365.71 mol/L) was significantly lower than that of the control (2270.26 mol/L). However, shiitake diets did not significantly affect the levels of serum polar lipids in female rats.
TL;DR: In this article, weanling rats were fed AIN-93G diets made with casein or rice protein isolate (RPI) for 14 d, and the effects of RPI feeding on hepatic PPARgamma signaling were significant but less robust.
Abstract: In order to understand the molecular mechanisms underlying effects of feeding rice protein on lipid and glucose homeostasis, weanling rats were fed AIN-93G diets made with casein or rice protein isolate (RPI) for 14 d. Peroxisome proliferator-activated receptor (PPAR)alpha genes and proteins involved in fatty acid degradation were upregulated by feeding RPI (P < 0.05), accompanied by increased promoter binding and nuclear expression of PPARalpha and its heterodimerization partner retinoid X receptor (P < 0.05). Effects of RPI feeding on hepatic PPARgamma signaling were significant but less robust. Feeding RPI also increased hepatic genes involved in cholesterol metabolism and transport. However, feeding RPI had no effect on binding of liver X-receptor (LXR)alpha to the cytochrome P450 (CYP)7A1 promoter. The effect of RPI feeding on PPARalpha signaling appeared to be direct and was reversed when RPI diets were switched to casein. In another experiment, male Sprague-Dawley rats were fed casein diets from postnatal day (PND) 24 to PND64 or were fed high fat 'Western' diets containing 0.5% cholesterol made with either casein or RPI. Increased liver triglyceride content, hypercholesterolemia and insulin resistance in the 'Western' diet-fed rats were partially prevented by feeding RPI (P < 0.05). mRNA and protein expression of hepatic enzymes involved in fatty acid synthesis were suppressed by feeding 'Western diets' containing RPI (P < 0.05), despite a lack of effects on nuclear concentrations of sterol regulatory element binding protein-1c. These data suggest that attenuation of metabolic syndrome observed in RPI-fed rats after consumption of diets high in fat and cholesterol occur as a result of improved lipid and glucose homeostasis partly as a result of activation of PPARs.