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Introduction to Nutrigenomics

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Uterus, testis, pituitary, ovary, epididymis, and adrenal gland. ER-b (Kuiper et al. 1996) brain, kidney, prostrate, ovary, lung, bladder, intestine, and epididymis. ... – PowerPoint PPT presentation

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Title: Introduction to Nutrigenomics


1
Introduction to Nutrigenomics
  • Lecture 22
  • April 14, 2008
  • Dr. Quadro

2
Improper diets are risk factors for diseases
  • Epidemiological studies associate specific foods
    with incidence and severity of obesity, diabetes,
    cardiovascular, cancer and/or other chronic
    diseases.

3
Nutrigenomics
  • The study of the effects of diet on the activity
    of individuals genes and health

4
  • Dietary constituents can affect gene expression
    and/or genome structure

Effects on -Transcription -DNA structure
5
Structure of Cells
  • Plasma membrane
  • Cytoplasm
  • Nucleus (compartment where DNA is stored)

6
Functions of Nucleus
  • Keeps the DNA molecules of eukaryotic cells
    separate from metabolic machinery of cytoplasm
  • Makes it easier to organize DNA and to copy it
    before parent cells divide into two daughter
    cells

7
Deoxyribonucleic Acid (DNA)
Is the molecule of life It contains all the
information needed to build an organism The
genetic material
(http//siggy.chem.ucla.edu/tim/chemistry/DNA.jpg
)
8
Role of the genetic material
  • A genetic material must carry out two jobs
    duplicate itself and control the development of
    the rest of the cell in a specific way.
  • -Francis Crick

9
DNA is a chain of nucleotides
  • Nucleotides are composed of
  • -Sugar-deoxyribose
  • -Phosphate
  • -Base-one of four types adenine (A), thymine
    (T)
  • guanine (G),
    cytosine (C)

10
Structure of DNA
G
C
Two nucleic acid chains running in opposite
directions The two nucleic acid chains are
coiled around a central axis to form a double
helix For each chain the backbone comes from
linking the pentose sugar bases between
nucleotides The bases face inward and pair in a
highly specific fashion with bases in the other
chain A only with T, G only with C Because of
this pairing, each strand is complementary to the
other 5 ACGTC 3 3 TGCAG 5 
A
T
C
G
T
A
G
C
A
T
C
G
T
A
G
C
A
T
C
G
11
A gene molecular definition
  • A gene is a segment of DNA which codes the
    formation of RNA which in turn directs the
    formation of a protein.

Genotype the genetic information
Phenotype the external features
12
RNA is a chain of nucleotides
-Single chain of nucleotides
  • -Nucleotides are composed of
  • Sugar-ribose
  • Phosphate
  • Base-one of four types adenine (A), uracile
    (U)
  • guanine (G),
    cytosine (C)

13
Gene expression the flow of genetic information
from DNA via RNA to protein
14
The genetic information is coded by the sequence
of the nucleotides
RNA
Protein
The protein creates the phenotype
15
The genetic information is coded by the sequence
of the nucleotides
RNA
Protein
16
Nutrigenomics
Diet
Health or Disease
17
Molecular nutrition
18
Many genes are regulated by dietthrough the
interaction of a given food component with a
specific receptor or set of receptors
Diet plays a crucial role in chronic diseases
19
..Again Transcription
Genes are flanked by untranscribed regions called
Promoters. This are DNA sequences near the
beginning of genes that signal RNA polymerase
where to begin transcription
20
Transcriptional regulation by vitamin A
RAR
RXR
Gene of interest
RARE
PROMOTER
21
Transcription-factor pathways mediating
nutrient-gene interaction
22
Functions of PPARs
PPARa
PPARg
PPARb
  • Nutrient metabolism
  • (lipid, glucose, AAs)
  • - Proliferation
  • - Inflammation

- Lipid and glucose metabolism - Cell cycle
control - Inflammation
- Lipid metabolism - Keratinocyte
differentiation - Inflammation
23
PPARs are ligand activated transcription factors
Function
9 cis retinoic acid
fatty acids
PPAR
Proteinsynthesis
-

PPAR
RXR
DNA transcription
Gene
AGGTCAaAGGTCA
Response element
24
Why are PUFAs healthy?
SREBP1SP1/NF-Y
PPAR

-
Fatty acid oxidation genes
Lipogenic genes
FA synthesisTriglyceride synthesis
b-Oxidation
VLDL-TG
25
Estrogen Receptors
26
Estrogen Receptors
  • ER-a
  • Uterus, testis, pituitary, ovary, epididymis, and
    adrenal gland.
  • ER-b (Kuiper et al. 1996)
  • brain, kidney, prostrate, ovary, lung, bladder,
    intestine, and epididymis.
  • Membrane localized ER (Pietras and Szego, 1997)
  • ER-a and b differ in C-terminal ligand binding
    domains and N-terminal transactivation domains.
    Highest homology in DNA binding domain.

27
ER effects on different cell types
28
Phytoestrogens
Aherne and OBrien, 2002. Nutrition 1875-81.
29
Dietary Sources of Phytoestrogens
30
Soy Phytoestrogens
  • Genistein, daidzein, coumesterol, and equol bind
    to and transactivate both ER-??and ER-?
    (0.1-10mM)
  • Genistetin has a higher affinity for ER?.
  • Soy PEs effect cell cycle progression, growth,
    and differentiation. Have antioxidant and
    antiangiogenic activities.

31
Phytoestrogens in Human Health
  • Cancer prevention
  • Post-menopausal supplement
  • Prevention of osteoporosis
  • Cardiovascular health
  • Fertility
  • Breast enhancement

References Kurzer, 2003. J. Nutr. 133
1983S-1986S. Benassayag, et al., 2002. J.
Chromatogr.B 777233-248.
32
Nutrigenomics
  • Nutrigenomics attempts to study the genome-wide
    influences of nutrition.
  • From a nutrigenomics perspective, nutrients are
    dietary signals that are detected by the cellular
    sensor systems that influence gene and protein
    expression and, subsequently, metabolite
    production.
  • Patterns of gene expression, protein expression
    and metabolite production in response to
    particular nutrients or nutritional regimes can
    be viewed as 'dietary signatures'.
  • Nutrigenomics seeks to examine these dietary
    signatures in specific cells, tissues and
    organisms, and to understand how nutrition
    influences homeostasis.
  • Nutrigenomics aims to identify the genes that
    influence the risk of diet-related diseases on a
    genome-wide scale, and to understand the
    mechanisms that underlie these genetic
    predispositions.

Müller M,  Kersten S. Nutrigenomics Goals and
Perspectives. Nature Reviews Genetics 4, 315 -322
(2003)
33
Nutrigenomics
FoodsNutrition
Target GenesMechanismsPathways
SignaturesProfilesBiomarkers
Molecular Nutrition Genomics
NutritionalSystems Biology
  • Identification of dietary signals
  • Identification of dietary sensors
  • Identification of target genes
  • Reconstruction of signaling pathways
  • Measurement of stress signatures
  • Identification of early biomarkers

Large research consortiaBig money
Small research groupsSmall budgets
Complexity
34
  • Influence of diet on health depends upon an
    individuals genetic makeup

Personalized nutrition- diets based upon
genotype, nutritional requirements and
status It prevents and mitigate chronic
diseases
35
Personalized diets?
36
Diet and genes
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