Nutritional

Epigenomics:
What your
grandmother
didnt tell you
about nutrition!
2002 Davis Bioscience Group
The link between food and health is
well documented
But people still struggle to find the
right balance between energy intake
and energy expenditure.
The public is looking for disease
preventing and health promoting
foods and beverages that match
their lifestyles, cultures and genetics.
Evidence for the trans-generational
impact of epigenetics on health is
beginning to emerge.
Nutritional genomics is providing
new insights into diet-genome
interactions that will enable us to
achieve optimal health and well-being
earlier, and maintain it longer.
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
 NCMHD
Center of Excellence for
Nutritional Genomics

Nutrition
Health Food
Nutritional
Genomics
Markers Diet x Gene

Social/Cultural
Genomics Context

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Nutritional Genomics:
Definition

The study of those positive and negative diet-genome

interactions that over time, can affect health outcomes.
Nutrigenetics: Genetic variation (i.e., SNPs, CNVs,
VNTRs) that can affect how nutrient and non-nutrient
bioactives are assimilated, partitioned and utilized to
impact metabolism and physiology
Nutrigenomics: Diet-induced changes in gene
expression that can influence network interactions
and cellular information flow and
Nutritional epigenomics: Diet-informed epigenetic
modifications of chromatin (DNA methylation and
histone acetylation) that can alter gene function and
long term health outcomes

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 NCMHD
Center of Excellence for
Nutritional Genomics

Nutrition like shoes,

one size does not
fit all.

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Bioactive Components of
Fruits and Vegetables

Lutein Liminoids
isoflavones
lycopene

Quercetin proanthocyanidins
glucosinolates

Turmeric fiseten

catachins Resveratrol

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 Exactly how foods reduce
cancer risk is still not known

2007
Estimates of the preventability of
cancer by means of food and
nutrition and associated factors is 30
to 40%. Higher consumption of
several plant foods probably
protects against cancers of various
types.

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Now that we know what food is, we
need to know what food does?

Dietary Signals Mechanism? Health

Macronutrients
Micronutrients
Antioxidants
Outcomes
Essential Vitamins and Minerals Health
Phytochemicals (bioactives) Enzyme co-factors Longevity
Xenobiotics Pathophysiologies
Gene expression Disease
Death
(epigenetics)

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 Many factors filter and
modify human genetic potential

Life span

Because of these filters, we are not slaves to our genes

nor are we victims of genetic determinism.
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
NCMHD
Center of Excellence for
Nutritional Genomics

Epigenetics (soft inheritance):

The ability to change gene
activity without changing
gene sequence (no mutations
involved).
Typical epigenetic affects
include DNA methylation (gene
silencing) and Histone
acetylation (gene activation)

January 6, 2010

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Chromatin: The natural form
of DNA in the cell

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Why so much interest in Epigenetics
and the Epigenome?

Epigenetic regulation
CCLHDN Asilomar thus facilitates
CA March 10, 2009 the integration of intrinsic signals
and environmental signals by using highly conserved enzymatic
machinery for (chromatin modification).
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
NCMHD
Center of Excellence for
Nutritional Genomics
DNA Methylation:
Enzymes and DNA Replication

Methylated DNA

Dnmt-1, maintenance DNA Replication

methylase

Dnmt-3a,b,
Hemi-methylated DNA de novo
methylase

DNA Replication
X
Royal Jelly
Unmethylated DNA

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

NCMHD
Center of Excellence for
Nutritional Genomics

The Fetal Origins (formerly the Barker) Hypothesis:

Fetal environmental exposures, especially nutrition, can
directly affect embryonic development and program
the child for adult health outcomes. D. Barker, 1986

Dr. David Barker Dutch Famine, 1944-45: 18 thousand dead

www.thebarkertheory.org/ Chinese Famine, 1959-60: 20-40 million dead

Early Nutrition Risk Phenotypes Disease

Experiences Obesity Phenotypes
Hypertension CVD
Insulin Resistance T2DM
Genomic imprinting or Cancer
programming Alzheimers

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 Can the Grandmaternal effect
explain transgenerational disease?

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

NCMHD
Center of Excellence for
Nutritional Genomics

Epigenetic programming in utero of adult risk

factors and diseases as a function of maternal
protein restriction, low birth weight and
postnatal overfeeding:

Obesity
Impaired glucose tolerance
Glucose intolerance
Pancreatic cell dysfunction Dr. Susan Ozanne,
Insulin resistance University of Cambridge, U.K
Type 2 diabetes

Poor early growth and excessive adult calorie intake independently and additively affect mitogenic signaling and increase
mammary tumor susceptibility. 2010. Fernandez-Twinn et al. Carcinogenesis

Maternal protein restriction affects gene expression profiles in the kidney at weaning with implications for the regulation
of renal function and lifespan. 2010. Chen et al., Clin. Sci. (London), 119:373-84.

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 NCMHD
Center of Excellence for
Nutritional Genomics

Epigenetics: A transducer of dietary input and a

memory of environmental experiences.

Axin Fusion Mutation Axin Fusion Mutation Axin Fusion Mutation

No folate Low folate High folate

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 Epigenetic Reprogramming by DNA
Methylation Gene Silencing

IAP kinky tail

Gene X AxinFu Gene Gene Y Gene Z

normal tail (with

full methylation)
IAP

Gene X AxinFu Gene Gene Y Gene Z

Waterland et al. genesis 44:401-406 (2006)

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

NCMHD
Center of Excellence for
Nutritional Genomics

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 1-Carbon Metabolism Links Diet to
DNA methylation in several ways

Choline
(betaine)

Ulrich CM, Robien K, Sparks R. Pharmacogenomics and folate metabolism - a promising direction. Pharmacogenomics 2002; 3 (3): 299 - 313.

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

NCMHD
Center of Excellence for
Nutritional Genomics

Methyl-Bobby
January 6, 2010

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Health consequences of
losing epigenetic marks

Nature Genetics March 13, 2005

NH2XXXGKGGKGLGKGGAKRHRKVLR
1 8 16 20
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
NCMHD
Center of Excellence for
Nutritional Genomics

Diet-Influenced Epigenetic Control of Cancer

Preventing Genes by the Chromatin Binding Soy
Peptide, Lunasin

lunasin
4.7kD

NAIST, December 14, 2009

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Soy-rich diet are associated with
reduced cancer risk

Lunasin is a small peptide found in the

BBI concentrate (BBIC) that has been
shown to be chemopreventive in cell
cultures and small animal models.
Lunasin inhibits oncogene and BBI
carinogen-induced human cell 8kD
transformation. lunasin
4.7kD
Lunasin upregulates tumor suppressor
and another cancer-preventing genes Bowman-Birk Inhibitor
in human cells Concentrate

Galvez et al., Cancer Research (2001) 61:7473-78; Magbanua et al., Nutritional Genomics (2006) p.255-72

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Working Model for Lunasin Action

Non-Tumorigenic State

lunasin Nuclear HATs,

4.7kD P300-PCAF

H4-NH2XXXGKGGKGLGKGGAKRHRKVLR
5 8 12 16 20

Hypoacetylated 30 nm chromatin Hyperacetylated 10 nm beads -

fibers - transcriptionally inactive transcriptionally active

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Health consequences of
losing epigenetic marks

Nature Genetics March 13, 2005

NH2XXXGKGGKGLGKGGAKRHRKVLR
1 8 16 20
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
Importance of Diet on Epigenetics

There are many dietary ingredients with epigenetic

and chromatin remodeling properties

Sulforaphanes from Brassica HDAC inhibitors

EGCG from green tea DNA demethylation
Genistein from soy DNA methylation/demethylation
Resveratrol from red grapes affects NAD+- dependent
histone deacetylases (i.e., SIRT1) that deacetylates
histones and regulatory proteins like PGC-1
Lunasin from soy chromatin binding peptide that
promotes histone acetylation

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

Relevance of Epigenetics to
Nutrition and Health

Diet can alter the epigenetic state of the genome leading

to dramatic deprogramming or reprogramming of large
numbers of genes in metabolic pathways and physiological
systems.

This may affect the incidence of late-stage, long-

latency, diseases such as type 2 diabetes, cardiovascular
disease, neurodegenerative disease and cancer.

Foods contain many inhibitors and stimulators of

chromatin remodeling enzymes (DNA methylases and
histone acetylases and deacetylases), making nutritional
intervention a possible way to reprogram the
epigenome to promote health and prevent disease.

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

NCMHD
Center of Excellence for
Nutritional Genomics

Dont blame your

genes or your
epigenome! It was
the one advantage
you had over your
genetic heritage
and you blew it.
Methyl-Bobby
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
 NCMHD
Center of Excellence for
Nutritional Genomics

Good nutrition is the cornerstone of

health and disease prevention but
good nutrition comes at a price.
As people in developed countries
grow increasingly older, fatter and
sicker, dietary intervention will play
an increasing role in the prevention
and treatment of disease.
Nutritional genomic products and
services should be accessible to all,
particularly those who need it the
most, vulnerable groups, the poor
and uninsured.
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
 NCMHD
Center of Excellence for
Nutritional Genomics

You are what you eat.

You are what your mother

ate.

You are what your

grandmother ate.

You are what your

microbiome ate.
Giuseppe Arcimboldo

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 Can the Grandmaternal effect
explain transgenerational disease?

National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu

 NCMHD
Center of Excellence for
Nutritional Genomics

Nutritional genomics represents

a new approach for translating
the exciting discoveries of
genomic research into
appropriate actions for using
nutrition to prevent disease and
promote health for individuals,
families, and communities. But
there are no shortcuts.
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu
 NCMHD
Center of Excellence for
Nutritional Genomics

Remember, before there were

drugs, there was food!

www.newslaugh.com/index051406.html

Thank you
National WIC Conference September 23, 2010 http://nutrigenomics.ucdavis.edu