Barger J.L.,Lifegen Technologies, Llc |
Kayo T.,Lifegen Technologies, Llc |
Pugh T.D.,Lifegen Technologies, Llc |
Vann J.A.,Lifegen Technologies, Llc |
And 4 more authors.
Genes and Nutrition | Year: 2012
The essential trace mineral selenium is an important determinant of oxidative stress susceptibility, with several studies showing an inverse relationship between selenium intake and cancer. Because different chemical forms of selenium have been reported to have varying bioactivity, there is a need for nutrigenomic studies that can comprehensively assess whether there are divergent effects at the molecular level. We examined the gene expression profiles associated with selenomethionine (SM), sodium selenite (SS), and yeast-derived selenium (YS) in the intestine, gastrocnemius, cerebral cortex, and liver of mice. Weanling mice were fed either a selenium-deficient (SD) diet (<0.01 mg/kg diet) or a diet supplemented with one of three selenium sources (1 mg/kg diet, as either SM, SS or YS) for 100 days. All forms of selenium were equally effective in activating standard measures of selenium status, including tissue selenium levels, expression of genes encoding selenoproteins (Gpx1 and Txnrd2), and increasing GPX1 enzyme activity. However, gene expression profiling revealed that SS and YS were similar (and distinct from SM) in both the expression pattern of individual genes and gene functional categories. Furthermore, only YS significantly reduced the expression of Gadd45b in all four tissues and also reduced GADD45B protein levels in liver. Taken together, these results show that gene expression profiling is a powerful technique capable of elucidating differences in the bioactivity of different forms of selenium. © Springer-Verlag 2011.
Hiona A.,University of Florida |
Sanz A.,Tampere University of Technology |
Kujoth G.C.,University of Wisconsin - Madison |
Pamplona R.,University of Lleida |
And 13 more authors.
PLoS ONE | Year: 2010
Background: Aging results in a progressive loss of skeletal muscle, a condition known as sarcopenia. Mitochondrial DNA (mtDNA) mutations accumulate with aging in skeletal muscle and correlate with muscle loss, although no causal relationship has been established. Methodology/Principal Findings: We investigated the relationship between mtDNA mutations and sarcopenia at the gene expression and biochemical levels using a mouse model that expresses a proofreading-deficient version (D257A) of the mitochondrial DNA Polymerase y, resulting in increased spontaneous mtDNA mutation rates. Gene expression profiling of D257A mice followed by Parametric Analysis of Gene Set Enrichment (PAGE) indicates that the D257A mutation is associated with a profound downregulation of gene sets associated with mitochondrial function. At the biochemical level, sarcopenia in D257A mice is associated with a marked reduction (35-50%) in the content of electron transport chain (ETC) complexes I, III and IV, all of which are partly encoded by mtDNA. D257A mice display impaired mitochondrial bioenergetics associated with compromised state-3 respiration, lower ATP content and a resulting decrease in mitochondrial membrane potential (ΔΨm). Surprisingly, mitochondrial dysfunction was not accompanied by an increase in mitochondrial reactive oxygen species (ROS) production or oxidative damage. Conclusions/Significance: These findings demonstrate that mutations in mtDNA can be causal in sarcopenia by affecting the assembly of functional ETC complexes, the lack of which provokes a decrease in oxidative phosphorylation, without an increase in oxidative stress, and ultimately, skeletal muscle apoptosis and sarcopenia. © 2010 Hiona et al.
PubMed | University of Wisconsin - Madison, Lifegen Technologies, Llc and Nestlé
Type: Journal Article | Journal: Metabolites | Year: 2014
Calorie restriction (CR) has long been used to study lifespan effects and oppose the development of a broad array of age-related biological and pathological changes (increase healthspan). Yet, a comprehensive comparison of the metabolic phenotype across different genetic backgrounds to identify common metabolic markers affected by CR is still lacking. Using a system biology approach comprising metabonomics and liver transcriptomics we revealed the effect of CR across multiple mouse strains (129S1/SvlmJ, C57BL6/J, C3H/HeJ, CBA/J, DBA/2J, JC3F1/J). Oligonucleotide microarrays identified 76 genes as differentially expressed in all six strains confirmed. These genes were subjected to quantitative RT-PCR analysis in the C57BL/6J mouse strain, and a CR-induced change expression was confirmed for 14 genes. To fully depict the metabolic pathways affected by CR and complement the changes observed through differential gene expression, the metabolome of C57BL6/J was further characterized in liver tissues, urine and plasma levels using a combination or targeted mass spectrometry and proton nuclear magnetic resonance spectroscopy. Overall, our integrated approach commonly confirms that energy metabolism, stress response, lipids regulators and the insulin/IGF-1 are key determinants factors involved in CR regulation.
Bjorndal B.,University of Bergen |
Berge K.,Aker BioMarine ASA |
Barger J.L.,Lifegen Technologies, Llc |
Berge R.K.,University of Bergen |
Burri L.,Aker BioMarine ASA
Journal of Functional Foods | Year: 2014
The effect of krill powder, a mixed source of protein and n-3 polyunsaturated fatty acids from Antarctic krill (Euphausia superba), on hepatic gene expression was analyzed in CBA/J mice. Mice were fed a low-fat control diet or a 3% (w/w) krill powder low-fat diet for 3. months. Gene expression profiling on liver samples revealed that the krill powder supplemented diet modulated a large number of pathways compared to the control diet. Metabolic pathways that were down-regulated included β-oxidation, glucose metabolism, and amino acid catabolism. In contrast, the mitochondrial electron transport chain pathway was upregulated. Krill powder affected more pathways involved in protein metabolism than krill oil. Thus, a krill powder supplemented diet had potent and specific effects on energy metabolism and oxidative phosphorylation at the gene level. This indicates that krill powder supplementation could be an approach to prevent decline in mitochondrial respiratory chain function. © 2013 Elsevier Ltd.
Brennan K.M.,Alltech Inc. |
Brennan K.M.,University of Kentucky |
Crowdus C.A.,Alltech Inc. |
Cantor A.H.,University of Kentucky |
And 6 more authors.
Animal Reproduction Science | Year: 2011
Selenium (Se) is an essential component of at least 25 selenoproteins involved in a multitude of physiological functions, including reproduction. However, relatively little is known about the mechanisms by which Se exerts its physiological effects in reproductive tissue. The objective of this study was to compare the effect of long-term inorganic Se (sodium selenite, SS) and organic yeast-derived Se (Sel-Plex®, SP) supplementations on tissue Se content and gene expression patterns in the oviduct of broiler-breeder hens. Hens were randomly assigned at 6 weeks of age to one of the three treatments: basal semi-purified diet (control), basal diet+0.3ppm Se as SP or basal diet+0.3ppm Se as SS. At 49 weeks, oviduct tissue from hens randomly selected from each treatment (n=7) was analyzed for Se content and gene expression profiles using the Affymetrix Chicken genome array. Gene expression data were evaluated using GeneSpring GX 10.0 (Silicon Genetics, Redwood, CA) and Ingenuity Pathways Analysis software (Ingenuity Systems, Redwood City, CA). Oviduct Se concentration was greater with Se supplementation compared with the control (P≤0.05) but did not differ between SS- and SP-supplemented groups. Gene expression analysis revealed that the quantity of gene transcripts associated with energy production and protein translation were greater in the oviduct with SP but not SS supplementation. Targets up-regulated by SP, but not SS, included genes encoding several subunits of the mitochondrial respiratory complexes, ubiquinone production and ribosomal subunits. SS hens showed a decrease in transcripts of genes involved in respiratory complexes, ATP synthesis and protein translation and metabolism in oviduct relative to control hens. In this study, although tissue Se concentrations did not differ between hens fed SS- and SP-supplemented diets, expression patterns of genes involved in energy production and protein synthesis pathways differed between treatments. These variations may partially explain the differences in reproductive performance reported in hens fed different forms of Se. © 2011 Elsevier B.V.
Burri L.,Aker BioMarine ASA |
Berge K.,Aker BioMarine ASA |
Wibrand K.,University of Bergen |
Berge R.K.,University of Bergen |
Barger J.L.,Lifegen Technologies, Llc
Frontiers in Genetics | Year: 2011
Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil (FO) or krill oil (KO). We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (KO) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that KO-supplementation increases the activity of the mitochon-drial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from FO modulated fewer pathways than a KO-supplemented diet and did not modulate key metabolic pathways regulated by KO, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, FO upregulated the cholesterol synthesis pathway, which was the opposite effect of krill-supplementation. Neither diet elicited changes in plasma levels of lipids, glucose, or insulin, probably because the mice used in this study were young and were fed a low-fat diet. Further studies of KO-supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects. © 2011 Burri, Berge, Wibrand, Berge and Barger.
Barger J.L.,Lifegen Technologies, Llc
Annals of the New York Academy of Sciences | Year: 2013
Adipose tissue is an active endocrine organ that responds to changes in energy balance and influences whole-body physiology. Adipose tissue dysfunction with obesity is associated with metabolic disease, neurodegeneration, inflammation, and cancer, whereas calorie restriction (CR) decreases both adiposity and disease risk. Although resveratrol does not affect obesity, it mimics long-term CR by increasing both life span in model organisms and health span in rodents. Because resveratrol's benefits in experimental animals are reminiscent of improved adipose tissue function under CR, this review synthesizes existing data to assess if resveratrol's effects may be mediated by mimicking CR in adipose tissue. In metabolically unhealthy humans, resveratrol consumption recapitulates the health benefits of CR, whereas short-term resveratrol in otherwise healthy humans mimics CR at the transcriptional, but not physiological, level. This latter observation (neutral effect of short-term resveratrol) may be protective against future disease risk; however, long-term studies in healthy humans will be needed to support this hypothesis. © 2013 New York Academy of Sciences.
Mallonee D.H.,Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition |
Crowdus C.A.,Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition |
Barger J.L.,Lifegen Technologies, Llc |
Dawson K.A.,Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition |
Power R.F.,Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition
Biological Trace Element Research | Year: 2011
Selenium is a trace element that, although toxic in higher concentrations, is essential for human and animal health. In this study, we looked at microarray-based gene expression patterns from liver and gastrocnemius tissues in mice fed either a selenium-deficient diet or diets containing sodium selenite, selenomethionine, or a yeast-derived selenium supplement. A p value cutoff of 0.01 was used to identify a select set of selenium-responsive genes that were consistently differentially expressed across three age groups of mice with both ANOVA and t test analyses. A total of 19 gene transcripts were found to be differentially expressed across the three age groups with at least one selenium-deficient/selenium-supplemented diet comparison. Of those 19 genes, 12 had been previously identified as selenoprotein-encoding genes, and four of the genes, Gpx1, Selh, Sep15, and Sepw1, were differentially expressed in both tissues, all three mouse age groups, and all three diet comparisons. Activities associated with non-selenoproteins encoded by selenium-responsive genes included transport and stress response. The selenophosphate synthetase 2 gene Sephs2 in gastrocnemius tissue and the solute carrier gene Slc48a1 in liver tissue, both up-regulated with selenium-deficient diets compared to all three selenium-supplemented diets, are previously overlooked candidates for dietary selenium marker genes. © 2010 Springer Science+Business Media, LLC.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 123.89K | Year: 2010
DESCRIPTION (provided by applicant): Calorie restriction (CR) is the only non-genetic intervention known to increase maximum lifespan and oppose a broad spectrum of age-related diseases including diabetes, sarcopenia, cardiovascular disease and cancer. A marked characteristic of animals subjected to CR is a reduction in both the amount and bioactivity of adipose tissue, an organ that has only recently been associated with the aging process. Because of the interrelationship between aging, calorie intake and adipose tissue, and because it is difficult for humans to adhere to a CR diet, there is a strong interest in identifying biomarkers of CR in adipose tissue which can be used for screening compounds that may mimic the effect of CR and oppose age-related disease. DNA microarray analysis is a powerful technique for obtaining a global profile of the expression of tens of thousands of genes in single experiment. However, microarray studies of long-term CR are expensive and time-consuming (gt3 years in mice). Another concern with microarray analysis in this context is that thousands of genes are changed in response to long-term CR, and the majority of these changes in gene expression are specific to the genetic background of the mouse strain being studied. For these reasons, microarray analysis is not be feasible for large-scale screening of compounds which may mimic the effect of CR. Successful completion of the proposed research will yield a small number of genes (5-15) that are differentially expressed by short-term CR in adipose tissue of multiple strains of mice. These genes will represent robust transcriptional biomarkers of CR in adipose tissue and will likely be relevant to human health. This panel of genes can be used in future studies for rapid screening of nutrients and drugs that may mimic the effect of CR in adipose tissue. PUBLIC HEALTH RELEVANCE: Numerous studies have shown that a calorie-restricted (CR) diet extends lifespan and prevents a broad spectrum of age-related diseases but it is extremely difficult for humans to adhere to this regimen. Thus, there is a great interest in identifying nutrients and drugs that would achieve the health benefits of a CR diet. The proposed research will use a novel approach to identify the most important genes that are modulated by a CR diet, and these genetic markers can be used in the future to rapidly test dozens of compounds that may have the ability to oppose age-related diseases.
PubMed | University of Wisconsin - Madison and Lifegen Technologies, Llc
Type: Journal Article | Journal: PloS one | Year: 2015
Aging is the most significant risk factor for a range of diseases, including many cancers, neurodegeneration, cardiovascular disease, and diabetes. Caloric restriction (CR) without malnutrition delays aging in diverse species, and therefore offers unique insights into age-related disease vulnerability. Previous studies suggest that there are shared mechanisms of disease resistance associated with delayed aging, however quantitative support is lacking. We therefore sought to identify a common response to CR in diverse tissues and species and determine whether this signature would reflect health status independent of aging. We analyzed gene expression datasets from eight tissues of mice subjected to CR and identified a common transcriptional signature that includes functional categories of mitochondrial energy metabolism, inflammation and ribosomal structure. This signature is detected in flies, rats, and rhesus monkeys on CR, indicating aspects of CR that are evolutionarily conserved. Detection of the signature in mouse genetic models of slowed aging indicates that it is not unique to CR but rather a common aspect of extended longevity. Mice lacking the NAD-dependent deacetylase SIRT3 fail to induce mitochondrial and anti-inflammatory elements of the signature in response to CR, suggesting a potential mechanism involving SIRT3. The inverse of this transcriptional signature is detected with consumption of a high fat diet, obesity and metabolic disease, and is reversed in response to interventions that decrease disease risk. We propose that this evolutionarily conserved, tissue-independent, transcriptional signature of delayed aging and reduced disease vulnerability is a promising target for developing therapies for age-related diseases.