Linking nutrition to genomics

Bauer, Matthias; Hamm, Anne C.; Pankratz, Michael J.

doi:10.1515/bc.2004.073

Cited by 17 publications

(7 citation statements)

References 14 publications

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“…Nutrigenomics is a powerful strategy for identifying genes that act in nutrientdependent pathways (4,34), and our studies represent a first step toward the identification of genes with hitherto unknown roles in cholesterol homeostasis. We show here that the expression of four Niemann-Pick genes-NPC1b and NPC2c, -d, and -e-is strongly dependent on the concentration of dietary cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Receptor DHR96 Acts as a Sentinel for Low Cholesterol Concentrations in Drosophila melanogaster

Bujold

Gopalakrishnan

Nally

et al. 2010

Molecular and Cellular Biology

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All eukaryotic cells have to maintain cholesterol concentrations within defined margins in order to function normally. Perturbing cholesterol homeostasis can result in a wide range of cellular and systemic defects, including cardiovascular diseases, as well as Niemann-Pick and Tangier diseases. Here, we show that DHR96 is indispensable for mediating the transcriptional response to dietary cholesterol and that it acts as a key regulator of the Niemann-Pick type C gene family, as well as of other genes involved in cholesterol uptake, metabolism, and transport. DHR96 mutants are viable and phenotypically normal on a standard medium but fail to survive on diets that are low in cholesterol. DHR96 mutants have aberrant cholesterol levels, demonstrating a defect in maintaining cholesterol homeostasis. Remarkably, we found that a high-cholesterol diet phenocopied the genomic profile of the DHR96 mutation, indicating that DHR96 resides at the top of a genetic hierarchy controlling cholesterol homeostasis in insects. We propose a model whereby DHR96 is activated when cellular cholesterol concentrations drop below a critical threshold in order to protect cells from severe cholesterol deprivation.

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Section: Discussionmentioning

confidence: 99%

Nuclear Receptor DHR96 Acts as a Sentinel for Low Cholesterol Concentrations in Drosophila melanogaster

Bujold

Gopalakrishnan

Nally

et al. 2010

Molecular and Cellular Biology

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“…Nutrigenomics is a developing field in science aiming at understanding how a diet interacts with gene expression to influence the balance between health and disease (12)(13)(14). The application of high-throughput genomic methods to nutrition studies could allow identification of coordinated groups of genes that contribute to the adaptation of the metabolic pathways (15). Using bioinformatic tools, such as the analysis of promoter sequences of the regulated genes, could help in identifying master regulators.…”

Section: Introductionmentioning

confidence: 99%

Changes in Gene Expression in Skeletal Muscle in Response to Fat Overfeeding in Lean Men

Meugnier

Bossu

Oliel

et al. 2007

Obesity

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Changes in gene expression in skeletal muscle in response to fat overfeeding in lean men. Obesity. 2007;15: 2583-2594. Objective: The adaptive mechanisms in response to excess energy supply are still poorly known in humans. Our aims were to define metabolic responses and changes in gene expression in skeletal muscle of healthy volunteers during fat overfeeding. Research Methods and Procedures: Eight lean young healthy men were given a diet rich in saturated fat with an excess of ϳ550 kcal/d for 4 weeks. Using oligonucleotide microarrays, gene expression changes in skeletal muscle were analyzed at Day 0, Day 14, and Day 28. Results: Fat overfeeding led to an increase in body weight (1.0 Ϯ 0.3 kg) and waist circumference (2.2 Ϯ 0.5 cm, p ϭ 0.005) and a significant decrease in fasting non-esterified fatty acid plasma levels (Ϫ29 Ϯ 5%, p ϭ 0.028). Respiratory quotient was significantly increased (0.84 Ϯ 0.01 to 0.88 Ϯ 0.02, p ϭ 0.034) and lipid oxidation rate tended to decrease. The expression of 55 genes was modified in skeletal muscle. The main pathways indicated a coordinated stimulation of triacylglycerol synthesis, inhibition of lipolysis, reduction of fatty acid oxidation, and development of adipocytes. Promoter analysis of the regulated genes suggests that sterol regulatory element binding proteins might be important players of the short-term adaptation to fat overfeeding in human skeletal muscle. Discussion: This combined metabolic and genomic investigation shows that fat overfeeding for 28 days promotes the storage of the excess energy in lean men and demonstrates the usefulness of a transcriptomic approach to a better understanding of the metabolic adaptation to changes in nutritional behavior in human.

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“…[72][73][74][75][76] More data on dose-and time-related patterns of gene expression changes are needed, 73 and issues concerning validation have to be taken into account carefully. 77 The development of real-life approaches are among the most enticing issues in toxicological research; the predictive power of approaches developed by ED toxicology may substantially benefit from cross-talk with other research fields, such as biology of nuclear receptors and transcription factors, 52,80 nutrigenomics, 81 etc. The aim is to underpin critical mechanisms within multifactorial events (such as, endocrine-related health disorders) in order to eventually strengthen the scientific bases of strategies for risk management and prevention.…”

Section: Discussionmentioning

confidence: 99%

Risk Assessment of Endocrine Disrupters

Mantovani

2006

Annals of the New York Academy of Sciences

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Endocrine disrupters (ED) represent a good challenge for experimental toxicology. In order to deal with several critical points relevant to risk assessment: (a) ED may induce long-term effects upon exposure in susceptible developmental phases, including postnatal life up to puberty; thus, efforts are required to refine testing strategies, for example, by supporting the two-generation rodent study with a comprehensive in vitro/in vivo screening battery; (b) due to the regulatory role of endocrine homeostasis, mechanisms of endocrine disruption may impact on immune, neurobehavioral, and reproductive development, as well as on susceptibility to cancer; (c) the potential multiple exposure to ED with common targets through diet and/or living environment calls for the development of models to understand mechanisms of interactions and effects of mixtures; and (d) last but not least, ED may interact with a number of factors related to differential vulnerability of individuals or population subgroups, including the intake of nutrients or bioactive food components. Besides reducing the chance for noxious chemicals to enter our life, toxicological research on mechanisms may also lead to the definition of possible biomarkers of exposure, effect, and susceptibility that may be further exploited in human health surveillance.

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Linking nutrition to genomics

Cited by 17 publications

References 14 publications

Nuclear Receptor DHR96 Acts as a Sentinel for Low Cholesterol Concentrations in Drosophila melanogaster

Nuclear Receptor DHR96 Acts as a Sentinel for Low Cholesterol Concentrations in Drosophila melanogaster

Changes in Gene Expression in Skeletal Muscle in Response to Fat Overfeeding in Lean Men

Risk Assessment of Endocrine Disrupters

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