PKK3206 Nutrigenomics.pdf

PKK3206 NUTRITIONAL GENOMICS Nurul Husna Shafie, PhD Dept. of Nutrition Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Copyright © 2018 McGraw-Hill Education. All rights reserved. No reprod...

PKK3206 NUTRITIONAL GENOMICS Nurul Husna Shafie, PhD Dept. of Nutrition Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Copyright © 2018 McGraw-Hill Education. All rights reserved. No reproduction or distribution without written consent of McGraw-Hill Education.  LEARNING OBJECTIVES Define nutritional genomics Differentiate between nutrigenomics and nutrigenetics Describe concept and application of nutrigenomics 2 Copyright © 2018 McGraw-Hill Education. All rights reserved. No reproduction or distribution without written consent of McGraw-Hill Education.  Nutritional Genomics Nutrigenomics studies the effects of nutrients on gene structure and expression; Nutrigenetics is the responses of specific genetic variations to nutrients Two sub definitions Two sides of a coin Dynamic cause–effect relationship between nutrition and the human genome (Mutch et al., 2005) Nutrition-Gene Interaction (Mechanism of action) 1. Direct interactions Nutrients, sometimes after interacting with a receptor, behave as transcription factors that can bind to DNA and acutely induce gene expression 2. Epigenetic interactions Nutrients can alter the structure of DNA so that gene expression is chronically altered 3. Genetic variation Common genetic variations such as single-nucleotide polymorphisms (SNPs) can alter the expression or functionality of genes  BIOACTIVE FOOD COMPONENTS: GENETIC, EPIGENETIC AND PROTEOMIC EFFECTS Epigenetic Milner J Nutr 2004 Nutrigenomics – A Systems BiologyApproach Health effects of the nutrient and non-nutrient components of food relates specific molecular interactions (Ommen et al., 2004) Bioactive food components influence genetic and epigenetic events associated with several cancer processes  Mechanisms by which nutrients influence gene expression: 1. Regulation of transcription factors and transcription process Bioactive food components promoter gene DNA Regulatory sequences in DNA mRNA Proteins: enzymes, receptors, transporters  Mechanisms by which nutrients influence gene expression: 2. Regulation of chromatin structure and DNA susceptibility to transcriptional machinery (how certain genes are switched on or switched off – nutri-epigenetics) Transcription possible Gene switched on: Active chromatin unmethylated cytosines Acetylated histones Gene switched off: Silent chromatin Methylated cytosines Deacetylated histones Transcription inhibited “Food and nutrition in 21st century”, Warsaw,8-9.09.2011  The two main components of the epigenetic labeling : A combination of Acetylation different molecules Methylation attached to the “tails” Phosphorylation of histones alters Histones DNA strand activity of the DNA wrapped around them. Histone modification DNA methylation: methyl marks added to Chromosome one DNA bases (cytosine) repress gene activity DNA methylation “Food and nutrition in 21st century”, Warsaw,8-9.09.2011 Dietary factors and the regulation of DNA methylation (epigenetics)  Folate -rich diet of mother- mouse results in methylation of the IAP sequence in the genome of the offspring and the agouti gene silencing. Result: brown color of child coat. Folate -deficient diet of mother-mouse results in hypomethylation of the IAP sequence and active agouti gene leads to a yellow coat color, obesity and tumors. A allele (wild type) Normal - brown Methylated AIAP allele Normal - brown Yellow color, Unmethylated AIAP allele obesity tumor susceptibility IAP D. C. Dolinoy, J. R. Weidman, R. A. Waterland, R. L. Jirtle: (2006) Environ Health Perspect 114: 567–572  Mechanisms by which nutrients influence gene expression: 3. Prevention of DNA damage Michael Fenech, CSIRO Preventive Health National Research Flagship Oxidative stress DNA strand breaks Lymphocytes with Calorie excess DNA hypomethylation damaged or unstable Nutrient deficiency or Telomere shortening genome excess The micronucleus assay in cytokinesis-blocked lymphocytes is currently the best validated biomarker for nutritional genomic studies of DNA damage. Moderate folate deficiency within the physiological range causes as much DNA damage in cultured lymphocytes as ten times the annual allowed limit of exposure to X rays Level of micronuclei indicates severe DNA damage The typical plasma folate concentration is only 10– 30 nmol/L, a level adequate to prevent anemia but insufficient to minimize chromosomal damage. Michael Fenech, CSIRO Preventive Health National Research Flagship  MICRONUTRIENT DEFICIENCY - DNA DAMAGE WITH HEALTH EFFECTS From: Kaput J: Physiol Genomics 2004 Ref 2: Ames, Toxicol Lett 1998  Health Effect of Dietary Fatty Acids and Transcription Factors (TFs) Fatty acids had important metabolic effects with respect to energy homeostasis, lipoprotein metabolism, glucose homeostasis and inflammation  Lipid sensitive transcription factors Interaction between lipid sensitive Transcription Factors (TF) PPARα activation regulation Expression of SREBP-1c & other downstream lipogenic genes (Clarke et al., 1999) EFFECTS OF SELENIUM ON CERTAIN GENES Cancer Res, 2002 INTER-RELATIONSHIP BETWEEN BIOACTIVE FOOD COMPONENTS AND EVENTS INVOLVED IN THE CANCER PROCESS  LC-PUFA: LONG CHAIN POLYUNSATURATED FATTY ACIDS A typical example of complex, bioactive molecules in nutrigenomics Epidemiological studies on LC-PUFA: Consumption of LC-PUFA beneficially affect physiological processes such as : - growth, neurological development, LC-PUFA: - lean and fat mass accretion, Long chain - reproduction, polyunsaturated fatty - Innate and acquired immunity, acids - infectious pathologies of viruses, Mutch, FASEB J 2005 - bacteria and parasites; - the incidence and severity of virtually all chronic - and degenerative diseases cancer, atherosclerosis, stroke, arthritis, diabetes, osteoporosis, and neurodegenerative, inflammatory and skin diseases MODERN NUTRIGENOMIC TECHNOLOGIES + BIOINFORMATICS CAN TO REVEAL THE COMPLEXITY OF LC-PUFA SIGNALING According to microarray studies: LC-PUFA can mediate the functions of several transcription factors, cell-cycle regulatory genes, RNA transcription processes, prostaglandin synthesis, inducible nitric oxide synthase and related proinflammatory genes BIOLOGICAL NETWORK TRIGGERED AFTER THE CONSUMPTION OF LC-PUFA LC-PUFA actions are mediated by transcription factors, such as PPAR and SREBP. Highlighted in blue are known functional and /or physical interactions between PPAR- and other genes Mutch, FASEB 2005 MODERN NUTRIGENOMIC TECHNOLOGIES + BIOINFORMATICS CAN TO REVEAL THE COMPLEXITY OF LC-PUFA SIGNALING: Further work: small inhibiting RNA technology, alternate analytical platforms (proteins, metabolites) etc. can clarify the biological functions, mediated by dietary lipids.