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
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.
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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).
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• 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.