1. FEEDING OUR GENES:
OMEGA-3 FATTY ACIDS
AND OUR GENES
C A R O L Y N M E Y E R
B E N E D I C T I N E U N I V E R S I T Y
2 0 1 6
2. LEARNING OBJECTIVES
UPON COMPLETION OF THIS PROGRAM, ATTENDEES WILL…
Review Genetic Basics: Our DNA and Coding Proteins
Understand the Basics of Gene Expression
Understand How Quality of Diet Can Change the Way
Genes Work
Understand What Types of Fat Consumed Can Affect
Gene Expression
Understand What Genes are Affected by DHA
(Docosahexaenoic acid)
Understand How these Genes Work Positively or
Negatively for our Health
Understand DHA recommendations
Understand How These Results affect the Practice of
Dietetics Now and in the Future
3. Gene Expression: What Does that Mean?
o Genetic Review
Genes are subunits of our DNA
DNA is the information database contained
inside the nucleus of our cells.
The DNA contains the genetic map that is
used to make all the proteins our cells
need.
Every gene contains a particular set of
instructions that code for a specific
protein.
4.
5. Gene expression is the process by
which genetic instructions are used
to synthesize gene products. 1
These proteins are then used to form enzymes,
hormones, and cell receptors; all perform
essential functions in our body.
o These genes create essential hormones
necessary for the way our bodies metabolize
nutrients and react to stress.
Mandal A. What is Gene Expression?. News-Medicalnet. 2009. Available at: http://www.news-medical.net/life-sciences/What-is-Gene-
Expression.aspx. Accessed May 6, 2016.
6. THE PROCESS OF GENE EXPRESSION INVOLVES TWO
MAIN STAGES
Transcription: the production of messenger RNA (mRNA) by
the enzyme RNA polymerase, and the processing of the
resulting mRNA molecule.
Translation: the use of mRNA to direct protein synthesis, and
the subsequent post-translational processing of the protein
molecule.2
Virtual Genetics Education Centre. University of Leicester. 2016. Available at: 2.
http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/topics/geneexpression-regulation.
Accessed May 6, 2016.
7.
8. CAN WE CHANGE OUR GENES?
Food Affects the Way our Genes Work
Quality of diet tends to affect the way our bodies produce
inflammatory and anti-inflammatory properties.
These anti-inflammatory and inflammatory properties are
produced in varying levels depending on the way its gene
precursor is expressed; more or less depending on the
gene’s expression.
increased release of inflammatory hormones are associated
with an increased risk for developing metabolic syndrome
and can lead to decreased insulin sensitivity.3
Beezhold, Complications of obesity, Powerpoint, 2015
9. GENE REGULATION AND THE FAT WE EAT
Omega-3 Fatty Acids are precursors of hormones
that regulate blood pressure, glucose
regulation, oxidative stress, and the anti-
inflammatory eicosanoids.
Omega-3 fatty acids are known to be
involved gene expression
Associated with down regulating fatty acid
synthesis
10. GENE REGULATION AND THE FAT WE EAT
Certain polyunsaturated fatty acids (PUFAs), like the
omega-3 PUFA’s, enhance hepatic fatty acid oxidation and
inhibit fatty acid synthesis and VLDL secretion.4
These hepatic functions are partially performed by
regulating gene expression.
The Study established that key transcription factors, like
PPARα, SREBP-1, ChREBP and MLX, are regulated by
omega-3 PUFA levels.4
Jump D, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and hepatic gene transcription. Chemistry and Physics of Lipids.
2008;153(1):3-13. doi:10.1016/j.chemphyslip.2008.02.007.
11. DHA-22:6,n-3: A 22 carbon strand fatty acid with
6 double bonds beginning on the 3rd carbon
classified as a long chain polyunsaturated fatty
acid.
PPARα- peroxisome proliferator activated
receptor: PPARs play essential roles in the
regulation of cellular differentiation, and
carbohydrate, lipid, and protein metabolism.4
Fatty acid oxidation
Jump D, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and hepatic gene transcription. Chemistry and Physics of Lipids.
2008;153(1):3-13. doi:10.1016/j.chemphyslip.2008.02.007.
12. SREBP-1- sterol regulatory element binding
protein: Lipid transcription factors for cholesterol
and fatty acid synthesis.5
ChREBP-carbohydrate regulatory element
binding protein: ChREBP is activated in response
to high glucose intake and up-regulates 15 genes
involved in the metabolic conversion of glucose to
fat (lipogenesis).6
A high fat diet inhibits ChREBP and slows
down the conversion of glucose to fat.
Shimano H. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Progress in Lipid Research. 2001;40(6):439-452.
doi:10.1016/s0163-7827(01)00010-8.
Uyeda K, Yamashita H, Kawaguchi T. Carbohydrate responsive element-binding protein (ChREBP): a key regulator of glucose metabolism and fat storage. Biochemical
Pharmacology. 2002;63(12):2075-2080. doi:10.1016/s0006-2952(02)01012-2.
13. MLX- max-like factor X: A transcription
regulator; a DNA-binding protein complex.
MLX plays a role in transcriptional activation
of glycolytic target genes in hepatic cells.7
Glucose responsive element binding
protein.8
MLX - Max-like protein X - Homo sapiens (Human) - MLX gene & protein. Uniprotorg. 2016. Available at: http://www.uniprot.org/uniprot/Q9UH92. Accessed
May 6, 2016.
Georgiadi AKersten S. Mechanisms of Gene Regulation by Fatty Acids. Advances in Nutrition: An International Review Journal. 2012;3(2):127-134.
14. DHA: DOWN-REGULATING OR UP-REGULATING
OUR GENES?
PPARα- peroxisome proliferator activated receptor:
DHA enhanced the activation of PPAR; up-
regulating of gene expression involved in fatty
acid oxidation.4
SREBP-1- sterol regulatory element binding protein:
omega-3 PUFAs found to suppress SREBP-1
therefor suppressing cholesterol and fatty acid
synthesis.4
Jump D, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and hepatic gene transcription. Chemistry and Physics
of Lipids. 2008;153(1):3-13. doi:10.1016/j.chemphyslip.2008.02.007.
15. DHA: DOWN-REGULATING OR UP-REGULATING
OUR GENES?
ChREBP-carbohydrate regulatory element
binding protein: ChREMP is down-regulated in
response to DHA consumption.4
Jump D, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and hepatic gene transcription. Chemistry and Physics of Lipids.
2008;153(1):3-13. doi:10.1016/j.chemphyslip.2008.02.007.
16. MLX- max-like factor X: MLX is down-regulated in
response to omega-3 PUFA consumption, not
specifically DHA alone.4
PUFAs reduce the expression of L-type pyruvate
kinase, which is involved in glycolysis in the liver,
by inhibiting translocation, or activation, of MLX.
Reduced Glycolysis
Jump D, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and hepatic gene transcription. Chemistry and Physics of Lipids. 2008;153(1):3-
13. doi:10.1016/j.chemphyslip.2008.02.007.
17.
18. WHY DHA?
22:6 Omega-3 suppresses the amount of ChREBP, MLX, and
SREBP-1 in the nucleus which in turn controls the expression
of glycolytic and lipogenic genes.
DHA’s main way of regulating gene expression is through its
effect on 26S proteosomal degradation of SREBP-1.
This is only found with 22:6 n-3 fatty acids (DHA); no other
PUFAs can control SREBP-1 nuclear abundance.
Jump D, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and hepatic gene transcription. Chemistry and Physics of Lipids.
2008;153(1):3-13. doi:10.1016/j.chemphyslip.2008.02.007.
19. HOW MUCH DHA?
The World Health Organization recommends a
daily EPA and DHA intake of 0.3-0.5 grams.9
The American Heart Association recommends 1
gram total of EPA and DHA daily for adults
diagnosed with Heart Disease.9
Omega-3 fatty acids, fish oil, alpha-linolenic acid. Dosing 2013. Available at: http://www.mayoclinic.org/drugs-supplements/omega-3-fatty-acids-fish-oil-alpha-
linolenic-acid/dosing/hrb-20059372. Accessed May 10, 2016.
20. RELEVANCE AS DIETITIANS
DHA is involved in up-regulating and down-regulating
of genes resulting in a positive outcome for our
health.
This change in gene expression can result in a
reduced risk for developing certain chronic
diseases.
• The prescription of the correct amount of DHA to
clients may improve the way hepatic cells function
leading to a reduced risk of certain common chronic
diseases and conditions.
21. References:
1. Mandal A. What is Gene Expression?. News-Medicalnet. 2009. Available at: http://www.news-
medical.net/life-sciences/What-is-Gene-Expression.aspx. Accessed May 6, 2016.
2. Virtual Genetics Education Centre. University of Leicester. 2016. Available at: 2.
http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/topics/geneexpression-
regulation. Accessed May 6, 2016.
3. Beezhold, Complications of obesity, Powerpoint, 2015
4. Jump D, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and
hepatic gene transcription. Chemistry and Physics of Lipids. 2008;153(1):3-13.
doi:10.1016/j.chemphyslip.2008.02.007.
5. Shimano H. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of
lipid synthetic genes. Progress in Lipid Research. 2001;40(6):439-452. doi:10.1016/s0163-
7827(01)00010-8.
6. Uyeda K, Yamashita H, Kawaguchi T. Carbohydrate responsive element-binding protein
(ChREBP): a key regulator of glucose metabolism and fat storage. Biochemical Pharmacology.
2002;63(12):2075-2080. doi:10.1016/s0006-2952(02)01012-2.
7. MLX - Max-like protein X - Homo sapiens (Human) - MLX gene & protein. Uniprotorg. 2016.
Available at: http://www.uniprot.org/uniprot/Q9UH92. Accessed May 6, 2016.
8. Georgiadi AKersten S. Mechanisms of Gene Regulation by Fatty Acids. Advances in Nutrition: An
International Review Journal. 2012;3(2):127-134. doi:10.3945/an.111.001602.
9. Omega-3 fatty acids, fish oil, alpha-linolenic acid. Dosing 2013. Available at:
http://www.mayoclinic.org/drugs-supplements/omega-3-fatty-acids-fish-oil-alpha-linolenic-
acid/dosing/hrb-20059372. Accessed May 10, 2016.
10. Mahan L, Escott-stump S, Raymond, J, eds. Krause’s food and the nutrition care process. St.
Louis, Missouri:Elsevier; 2012
Editor's Notes
This provides a general overview of our genetic makeup. DNA is formed into larger parts forming a gene that are then placed within our chromosomes within the cell nucleus.
As the previous slide discussed, genes are where instructions for specific proteins with particular functions are kept.
So we know the products formed from these genetic instructions are then formed into proteins.
Transcription is the first step in gene expression when the enzyme RNA polymerase is activated to create messenger mRNA.
Translation is the second step in gene expression where the messenger RNA, or mRNA, then is used to begin protein synthesis and determining how these protein molecules will be used in the body.
Why Does This Matter? This is the step where the protein molecule turned into a functional product for the body to use. This product can be used more actively by our bodies or used less; this is when a gene is expressed more profoundly or when activity is suppressed.
This provides an overall picture of the process involved with gene expression.
First the transcription begins, translation then leaves only the necessary units of amino acids that will then be used to form a complete amino acid chain that will be a finished protein.
We’ve established that food can change the way our genes function which then affect the way certain hormones function that can impact our health. But what foods change the gene functions that can positively affect our health?
1. The way we eat can either improve the metabolic functions of our body, or hurt these functions.
Certain hormones, which are produced through genes, are either activated or suppressed depending on the type of foods we eat.
The Type of Fat we eat can affect our genetic expression and therefore affect the way our metabolic pathways respond and function.
2. Read Slide
3. Metabolic alterations are due in part to lipid metabolism rather than excess energy intake
The inflammatory cascade that leads to insulin insensitivity leads to obesity issues
1. Last bullet point. A study completed in 2008 focused on DHA (Docosahexaenoic acid) and its effect on hepatic gene expression.
These genes control the level of proteins involved in lipid and carbohydrate metabolism.
1. PPAR alpha is a set of receptor proteins that function in regulating the expression of genes.
2. Read ppar bullet point
3. It also plays a role in controlling genes involved in fatty acid oxidation.
1. SREBP-1:Studies using knockout mice suggest that SREBP-1 seems to be involved in energy metabolism including fatty acid and glucose metabolism5
2. ChREBP-
ChREBP is able to control the transcription of lipogenic enzyme genes in response to nutritional and hormonal inputs.
This in turn may play an important role in disease states such as diabetes, obesity, and hypertension.6
Since the liver plays a central role in whole body carbohydrate and lipid metabolism, these regulatory factors impact whole body metabolism and contribute or inhibit the onset and progression of several chronic diseases, including atherosclerosis, diabetes and obesity.4
This means there is reduced transportation of MLX into the cell nucleus to modify gene expression resulting in reduced glycolysis.8
This provides a an overview of what is happening within our liver cells
You can see SREBP reduces fatty acid and cholesterol synthesis
MLX and ChREBP reduce glycolysis, glucose stored in the liver for later use
PPAR increases the catabolism of fatty acids;
we know these are all positive functions.
The results of this study were consistent with the findings that human diets supplemented with omega-3 PUFAs does not promote insulin resistance but impacts key downstream events.4
3. DHA inhibits the 26S proteasomal degradation of nuclear SREBP-1. Elevated nuclear content of SREBP-1 is one of the key factors involved in the positive effect of insulin on de novo lipogenesis. 22:6,n-3 antagonizes the insulin control of this process through novel pathways recently discovered. How every step of this is completed is still under investigation.4
So how much DHA should we be consuming in our diet for health benefits that could positively affect gene expression?
This can be found in
Salmon which provides (>1.5 grams EPA and DHA)
Albacore tuna provides (0.5 to 1 gram EPA and DHA)
Mackerel provides (1 to 1.5 grams EPA and DHA)
3. These conditions includes metabolic syndrome, decreased insulin sensitivity leading to diabetes, and increased lipogenesis and reduced fatty acid oxidation leading to heart disease and stroke.10
5. The recent findings of DHA and its effect on gene expression in hepatic liver cells suggest that other nutrients or components of certain foods could also positively affect target gene expression leading to reduced risk of other disease states leading to improved health and reduced risk of morbidity and mortality.
Mahan L, Escott-stump S, Raymond, J, eds. Krause’s food and the nutrition care process. St. Louis, Missouri:Elsevier; 2012
