1. Nutrigenomics
By: Clinical Dietitian II :
Samar AlDhamadi

2. Introduction
Gene, Nutrient and Gene Expression
Studies Review
Conclusion and Recommendations4
1
2
3
Contents

3. Genes are important in
determining a function, but
nutrition is able to modify the
degree of gene expression. 1

4. Archibald Garrod 1857-1936
♂ Diet would influence disease differently in different
individuals.2

5. Human Genome Project (HGP)
♂ On Monday 26th
of July 2000 was the launch of the initial version of the human
gene map, which contains 90% of the symbols of the map with the participation
of former U.S. President Bill Clinton and former British Prime Minister Tony
Blair. 3

6. Introduction
Nutritional Genomics 2
+
Nutritional
Genomics
Nutrigenomics
Nutrigenetics
Nutrigenetics:
Is about genes acting on diet
and other environmental
factors.
Nutrigenomics:
Is diet and other environmental
factors acting on genes,
changing expression.

7. Common dietary chemicals act on the human
genome, either directly or indirectly, to alter
gene expression or structure.1
2
Under certain circumstances and in some
individuals, diet can be a serious risk factor
for a number of diseases.
Cont
Nutrigenomics 4

8. Some diet-regulated genes (and their normal,
common variants) are likely to play a role in the
onset, incidence, progression, and/or severity of
chronic diseases.
3
4
5
The degree to which diet influences the balance
between healthy and disease states may depend
on an individual’s genetic makeup.
Dietary intervention based on knowledge of
nutritional requirement, nutritional status, and
genotype (i.e., “personalized nutrition”) can be
used to prevent, mitigate, or cure chronic disease.
Cont
Nutrigenomics 4

9. Psychological
stress
Oxidative
Stress
Inflammatory
Stress
Metabolic
Stress
Cont
Hypothesize that all diseases can be reduced to imbalances in
four overarching processes: 5
Diseases arise because of genetic predispositions to one or
more of these stressors. Nutrigenomics represents a major
effort to improve our understanding of the role of
nutrition and genomic interactions in at least the first
three of these areas.

10. Cont
Dietitian? What will this offer you? 6
 Diet plans and foods tailored to people
genetic makeup.
 Increased confidence that a particular
food recommendation will actually work.
 Accurate counseling that will modify
and reduce personal risk.

11. A chemical made up of 3 components:
Phosphorus
Ribose Nitrogenous
base
Gene, Nutrient and Gene Expression
DNA, Chromosomes, and Genes 4

12. ♂ Make up 4 different nucleotides, the
building blocks of nucleic acids (DNA and
RNA)
♂ Nucleotides are connected –end to end-
to create a very long linear molecule
(“strand”)
♂ DNA has two strands held together by
weak binding between pairs of bases
(A-T, C-G)
♂ The structure resembles a twisted rope
ladder, a structure called a “double helix”
Gene, Nutrient and Gene Expression
DNA, Chromosomes, and Genes4

13. Gene, Nutrient and Gene Expression
What is a gene? 4
♂ The nucleotide sequence of DNA holds information for making
proteins; this information is in code.
♂ A gene is a linear sequence of nucleotides whose encoded
information results in a protein (enzyme, receptor, hormone,
transporter, communicator, etc.)
♂ The total genetic code of all of the DNA on all the
chromosomes is the genome.
♂ The human genome is composed of 23 distinct pairs of
chromosomes (22 autosomal + X + Y) with a total of
approximately 3 billion DNA base pairs containing an
estimated 20,000–25,000 genes.

14. Gene, Nutrient and Gene Expression
Decoding Genetic Information 4
Transcription Translation
Post
-translationa
l processing
The nucleotide sequence must be decoded before it is useful to the cells
Decoding occurs in stages:
- From DNA into messenger RNA
(mRNA).
- From mRNA into amino acid
sequence of the protein.
- Protein may be modified
(e.g., glycosylated), cleaved.

15. Gene, Nutrient and Gene Expression
Genotype VS Phenotype? 4
Genotype is the sum total of
the information in our genes.
Phenotype is the expression
of that information.
Genotype
Phenotype

16. Gene, Nutrient and Gene Expression
Nutritional Genomics 4
Environment
+
Genotype
PHENOTYPE

17. Gene, Nutrient and Gene Expression
Genotype VS Phenotype? 4
The
expression of
that score - the
music - which
varies
depending on
the conductor.
Phenotype
Genotype
Analogy
Is like a
musical score

18. Gene
Changes in the Genetic Material 7
 It is a simple change in one base of the gene
sequence.
 There is one or more bases are inserted or
deleted. This type of mutation can make the
DNA meaningless & often results in a shortened
protein.
Point mutation
Frame-shift
mutation
Deletion
 Result in missing DNA. It can be small or longer
deletions that affect a large number of genes
on the chromosome.
 Deletions can also cause frame-shift mutations.

19. Gene, Nutrient and Gene Expression
Changes in the Genetic Material 7
 It result in the addition of extra DNA .
 It can cause frame-shift mutations &
general result in a nonfunctional protein.
Insertion
Inversion
 An entire section of DNA is reversed.
 A small inversion may involve only a few
bases within a gene, while longer
inversions involve large regions of a
chromosome containing several genes.

20. Studies Review

21. Fiber
Literature
Review
Studies Review
Protein
Carbohydrate
Calorie
Fat

22. Calorie
- Study investigate the effect of different low-
energy diets on gene expression in human
adipose tissue.
1.Both diets resulted in weight losses.
2.52 genes were up-regulated & 44 were down-
regulated.
Ingrid Dahlman. American Journal of Clinical Nutrition,. 2005

23. Cont
3. No major effect on:
- Lipid-specific transcription factors.
- Genes regulating signal transduction Lipolysis.
- Synthesis of acylglycerols.
4. All genes regulating formation of PUFA FAs
were down-regulated (35–60%).
Ingrid Dahlman. American Journal of Clinical Nutrition,. 2005

24. Cont
- Macronutrients have secondary role in changes
in adipocyte gene expression after energy
restricted diets.
- Alteration after energy restriction is coordinate
reduction in the expression of genes regulating
the production of PUFA FAs.
Ingrid Dahlman. American Journal of Clinical Nutrition,. 2005

25. Cont
• Plasma lipoprotein levels are determined by:
Balance between lipoprotein production & clearance.
• A study done to identify physiological determinants of
plasma Angioprotein – Realated Protein 4 ANGPTL4
levels in humans, focusing on the effect of energy
restriction & plasma FFAs.
• Major variations in baseline plasma ANGPTL4 levels
between individuals.
KerstenSet al. Vascular Biology. 2009

26. Cont
CONCLUSION
Within an individual, plasma ANGPTL4 levels
remain stable throughout the day but increase
significantly in response to:
- Long term fasting.
- Chronic caloric restriction.
- Endurance exercise via elevated FFAs.
KerstenSet al. Vascular Biology. 2009

27. Carbohydrate
- Glucose & fructose are metabolized in the liver.
- When there’s too much sugar in diet, the liver converts it to lipid.
Scientists discovered that increased production of lipid:
1. Shut down a gene called SHBG (sex hormone binding globulin)
2. Reducing amount of SHBG protein in blood.
- SHBG protein plays a key role in controlling the amount of
testosterone & estrogen that’s available throughout the body.
Geoffrey Hammond. Journal of Clinical Investigation. 2007

28. Cont
- More Testosterone & Estrogen will be released
throughout the body, which associated with risk
of acne, infertility, polycystic ovaries & uterine
cancer in overweight women.
- Abnormal distribution the balance between
Estrogen & Testosterone, which associated with
the development of CVD.
Geoffrey Hammond. Journal of Clinical Investigation. 2007

29. Cont
- Low levels means:
The liver’s metabolic state is out of whack. because of
inappropriate diet or something inherently wrong with the
liver long before there are any disease symptoms too
much insulin ↓ SHBG which come up from observation
over weight & pre-diabetic .
- The study proves :
Insulin isn’t blame & that it’s actually the liver’s metabolism
of sugar .
Geoffrey Hammond. Journal of Clinical Investigation. 2007

30. Cont
CONCLUSION
Uses of SHBG :
1. As a biomarker for monitoring liver function well before
symptoms arise.
2. For determining the effectiveness of dietary
interventions & drugs aimed at improving the liver’s
metabolic state.
3. To indicate an individual’s risk for developing type 2 DM
& CVD.
Geoffrey Hammond. Journal of Clinical Investigation. 2007

31. Cont
The main objective of study was to test 2 different CHO
modification:
- A rye-pasta diet characterized by low postprandial insulin
response .
- An oat-wheat-potato diet characterized by high
postprandial insulin response affect gene expression in
Subcutaneous Adipose Tissue SAT in persons with the
metabolic syndrome.
Petteri Kallio, American Journal of Clinical Nutrition. 2007

32. Cont
As result
- 71 down-regulated genes in the rye-pasta group,
including genes linked to insulin signaling & apoptosis.
- 62 genes up-regulated in the oat-wheat-potato diet
related to stress, cytokine mediated immunity&
interleukin pathway.
- Body weight was unchanged in both groups.
- Dietary CHO modification with rye or oat differentially
changes the gene expression profile in abdominal SAT,
even in the absence of weight loss.
Petteri Kallio, American Journal of Clinical Nutrition. 2007

33. Protein
Rats adapted to high protein exposure show an increased:
- AA & fat oxidation.
- Lower feed energy efficiency.
Dietary protein level can affect gene expression of
Uncoupling protein (UCP) homologues which is
suggested to be involved in:
- Thermogenesis.
- Substrate oxidation.
- Energy expenditure.
Petzke, K. J.,European Journal of Nutrition. 2006

34. Cont
- The results indicate that hepatic UCP2 &
Brown Adipose Tissue BAT UCP1 mRNA
expression is related to the level of dietary
protein intake.
- This suggests a role of UCPs in substrate
oxidation & in thermogenesis under
conditions of HP exposure.
Petzke, K. J.,European Journal of Nutrition. 2006

35. Fat
- A study investigates the effect of a short-term nutritional intervention
on gene expression in adipose tissue from lean & overweight
subjects.
- Gene expression profiles were measured after consumption of
PUFA FAs, conjugated linoleic acid & MCT & a control spread 40g of
fat daily for 9 days.
- Adipose tissue gene expression profiles of lean & overweight
subjects were different, mainly with respect to defense response &
metabolism.
MarjanJ. van Erk, Genes Nutr. 2008.

36. Fat
Results
- Lower expression of genes related to energy
metabolism in lean subjects.
- Expression of inflammatory genes was down-
regulated.
- Expression of lipid metabolism genes was up-
regulated in overweight subjects.
MarjanJ. van Erk, Genes Nutr. 2008.

37. Conclusion
- Nutrition has the most important life-long environmental
impact on human health.
- While nutrigenetics addresses how an individual's
genetic makeup predisposes for dietary susceptibility,
nutrigenomics asks how nutrition influences the
expression of the genome.
- These genetic changes may lead to alterations in
absorption, metabolism, and functional responses to
bioactive nutritional factors.

38. Cont
- Diet can affect the expression levels of genes by acting on
transcription factors or by causing structural changes.
- A large number of studies have clearly shown that nutrients alter the
expression of genetic information at the level of gene regulation,
signal transduction, and through alterations of chromatin structure
and protein function such as enzymes.

39. Recommendations
- It is serving dietetics professionals to recognize that an individual's
response to dietary intervention will depend on his or her genetic
background & may be used to promote human health & disease
prevention.
- In future its expected that Nutrigenomics will be the basic for
individual intake.
- More research & Scientist in this filed needed.
- Association ;The European Nutrigenomics Organization NuGO.
- Conferences & courses needed.

40. Thank You!