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NUTRIGENOMICS Mireia Viñas Genomics

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NUTRIGENOMICS

Mireia Viñas

Genomics

Overview • Introduction • Nutrigenomics • Ethnic differences • Nutritive effects • Nutrigenetics • Nutrigenetics and disease • Conclusions

• Bibliography

Introduction

Nutrigenomics Influence of nutrients in gene expression

Nutrigenetics Impact of genetic profile in the body response

Farhud et al.

Introduction

• Dietary chemicals act on the human genome to alter gene expression

• On specific conditions and certain individuals, diet represent a risk factor for some diseases

• Diet-regualted genes act in different stages of chronic diseases

• Individual genetic background determines the degree at which diet mantains an equilibrium

• Dietary intervention to prevent, relieve or cure chronic diseases

Farhud et al.

Nutrigenomics • Integration of high-troughput genomic tools with nutrition

research

• Dietary effects on:

– Genome stability

– Epigenome alterations

– RNA and microRNA expression

– Protein expression

– Metabolite changes

Nutrigenomics

• Folate deficency uracil incorporation

• Uracil glycosylase DSB leading to abasic sites

• Oxidative stress + folate deficency

• Oxidated bases abasic sites and DSB

• Low folate conditions DSB within one cell divison

Bull and Fenech

Nutrigenomics

• Defects in DNA methylation:

– escessive telomere elongation

– Homologous recombination between telomeres

– Telomere fusion

Bull and Fenech

• Diet can cause epigenetic changes

• DNA methylation is dependent on bioactive food components

Nutrigenomics • Calorie-restricted organisms:

– live longer

– have increased resistance to disease

– physically age slower

– postpones many signs of aging

Luigi Fontana

Nutrigenomics

• mTOR inactivation attenuation of global protein synthesis and decrease cellular load of erroneously synthesized polypeptides

• TOR pathway influence in life span:

– Decreased TOR signaling extend life span of Caenorhabditis elegans (Vellai et al.)

– Overexpression of dominant negative allele of TOR extends life span of Drosophila (Kapahi et al.)

– Specific TOR inhibitor (Rampamycin) increase in life span of mice (Harrison et al)

Nutrigenomics • Diversity in the inherited genome between ethnic groups and

individuals nutrient bioavailability and metabolism

• Differences in food/nutrient availability and choices cultural, economical, geographical and taste perception

• Malnutrition affect gene expression mutations at gene or chromosomal level

Ethnic differences • Singapore variability in response to a diet (Chinese, Malays

and Asian Indians)

• Ethnic heterogeneity within homogeneous environments

Mak et al., Cutter et al.

Nutritive effects

• Availability of environmental nutrients:

– determinant of growth and survival

– optimal immune response

• Honey bees pollen nutrition influence longevity, sensitivity to pesticides and resistance to pathogens

• Digital gene expression (DGE) between pollen feeding in normal and sick bees (varroa-parasited)

Alaux et al.

Nutritive effects • Vitellogenin (Vg) egg production

and antioxidant functions

• Varroa parasitism decrease Vg levels in P+ but worst in P-

• Prophenoloxidase (PPO) insect immunity

• Varroa inhibition immunity supression, no pollen effect

• Drosophila ortolog spaetzle signalling pathway against fungi and bacteria

• Increased in V-P+ bees pollen enhance immune functions

Alaux et al.

Nutrigenetics • Glutatione peroxide gene Pro/leu at codon 198 increased

risk of lung cancer

• Manganese super oxide dismutase (MnSOD) Val/Ala high risk of breast cancer (Trujillo et al.)

• Methylene tetrahydrofulate reducatse (MTHFR) Ala/Val reduced risk for folate-related pathologies (Stover)

Nutrigenetics • Caffeine-coffee increased risk of heart attack and

myocardial infarction for carriers of slow activity of CYP1A2 isoform (El-Schemy)

• Apolipoprotein A-1 (APOA1) highly polimorphic coding gene with a specific SNP

• A allele increased HDL cholesterol

• APOA1 and HDL protective factors for cardiovascular disease

Mata et al., Ordova et al.

Nutrigenetics and disease

• Butyrate originated by bacterial fermentation in colorectal cancer cells

• Butyrate treatment induce apoptosis and inhibit proliferation

• Proteomics and gene expression identification of butyrate mechanisms

Apoptosis and proliferation in colorectal cancer cell lines in

response to increased butyrate concentration

Fenech et al.

Nutrigenetics and disease

• Inability to tolerate gluten-containing foods

• Carrying the gens does not determine disease development

• HLA-DQ (DQ2 and/or DQ8) genes necessary but not sufficient

• Apolipoprotein E cholesterol carrier in the brain

• Genetic variation in gene encoding apolipoprotein E4 risk for Alzheimer’s disease

• Development of preventing strategies for genetic predisposition people

Alzheimer Coeliac disease

McGough and Cummings

Nutrigenetics and disease

Arkadianos et al.

Obesity

Conclusions

• The ultimate aim of nutrigenomics is to understand how nutrition influences metabolic pathways and homeostasis and develop dietary-interventional strategies

• The genetic background, gender and life stage have an impact on nutritional requirements

• Responses between individuals to dietary changes differ considerably need to combine nutrigenetic-based advice and ‘omic’ biomarkers

• Intervention based on knowledge of nutritional requirement can be useful to prevent, mitigate or cure chronic diseases.

Bibliography • Farhud, Yeganeh and Yeganeh. Nutrigenomics and Nutrigenetics (2010). Iranian Journal Public Health,

vol. 39 nº 4; 1-14. • Bull and Fenech. Genome-health nutrigenomics and nutrigenetics: nutritional requirements or

‘nutriomes’ for chromosomal stability and telomere maintenance at the individual level (2008). Proceedings of the Nutrition Society, 67; 146-156.

• Fontana. The Scientific Basis of Caloric Restriction Leading to Longer Life (2009). Current Opinion in Gastroenterology 25; 144-150.

• Vellai et al. Genetics: Influence of TOR Kinase on Lifespan in C. elegans (2003). Nature 426, 620. • Kapahi et al. Regulation of Lifespan in Drosophila by Modulation of Genes in TOR Signaling Pathway.

Divison of Biology 156-29. • Harrison et al. Rapamycin Fed Late in Life Extends Lifespan in Genetically Heterogeneous Mice (2009).

Nature 460; 392-395. • Mak et al. Ethnic Differences in Acute Myocardial Infarction in Singapore. European Heart Journal 24;

151-160. • Cutter et al. Levels of Cardiovascular Disease Risk Factors in Singapore Following a National

Intervention Programme. Bull World Health Organ vol 79 nº 10. • Alaux et al. Nutrigenomics in Honey Bees: Digital Gene Expression Analysis of Pollen’s Nutritive Effects

on Healthy and Varroa-parasitized Bees (2011). BMC Genomics 12: 496. • Dey. Molecular Mechanism-based Model to Enhance Outcomes of Dietary Intervention Studies for

Disease Prevention (2012). Journal of Molecular Biochemistry 16; 1(3): 150-154. • Fenech et al. Nutrigenetics and Nutrigenomics: Viewpoints on The Current Status and Applications in

Nutrition Research and Practise (2011). Journal of Nutrigenetics and Nutrigenomics 4; 69-89. • Ordovas et al. Polynsaturated Fatty Acids Modulate the Effects of G-A Polymorphism on HDL-

cholesterol Concentration in a Sex-specific Manner: the Framingham Study. Journal of Clinical Nutrition 75 (1); 38-46.

• McGough and Cummings. Coeliac Disease: a Diverse Clinical Syndrome Caused by Intolerance of Weat, Barely and Rye. Proceedings of the Nutrition Society 64, 434-450.

• Arkadianos et al. Improved Weight Management Using Genetic Information to Personalize a Calorie Controlled Diet (2007). Nutrition Journal 6:29.

Thank You for your attention!