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INTRODUCTION Nutrig enomics Dr. Muhamad Firdaus. Nutrig enomics The study of how naturally occurring chemicals in foods alter molecular expression of genetic information in each individual. When a gene is activated or expressed, a protein is produced.
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NutrigenomicsThe study of how naturally occurring chemicals in foods alter molecular expression of genetic information in each individual. When a gene is activated or expressed, a protein is produced
Gene expression patterns produce a phenotype, which represents the physical characteristics or observable traits of an organism, e.g., hair color, weight, or presence or absence of diseaseGenes alone do not necessary produce phenotypic traitsPhenotypic expression is influenced by nutrition
Nutrition-Gene Interaction 1. Direct interactionsNutrients, sometimes after interacting with a receptor, behave as transcription factors that can bind to DNA and acutely induce gene expression2. Epigenetic interactionsNutrients can alter the structure of DNA so that gene expression is chronically altered3. Genetic variationCommon genetic variations such as single-nucleotide polymorphisms (SNPs) can alter the expression or functionality of genes
BIOLOGICAL NETWORKS Intracellular regulations Cell-cell comuniacations Organ networks/homeostasis
MAIN HEALTH-RELATED CHALLENGES • Cardiovascular • Cancer • Diabetes-obesity • Undernutrition/malnutrition • Infectious diseases • Allergies • Ageing process
BIOACTIVE FOOD COMPONENTS CAN MODIFY TRANSCRIPTION, TRANSLATION AND METABOLISM
EFFECTS OF SELENIUM ON CERTAIN GENES Cancer Res, 2002
BIOACTIVE FOOD COMPONENTS:GENETIC, EPIGENETIC AND PROTEOMIC EFFECTS Milner J Nutr 2004
PARTIAL LIST OF BIOACTIVE FOOD COMPONENTS:WITH POSSIBLE EFFECTS ON CANCER
INTER-RELATIONSHIP BETWEEN BIOACTIVE FOOD COMPONENTS AND EVENTS INVOLVED IN THE CANCER PROCESS
FATE AND ACTIVITIES OF NUTRIENTS IN THE CELL may act directly asligands for transcription factor receptors (pathway A) Kaput J, Physiol Genomics 2004
FATE AND ACTIVITIES OF NUTRIENTS IN THE CELL may be metabolized bymetabolic pathways altering concentrations of substrates / intermediates (pathway B) Kaput J, Physiol Genomics 2004
FATE AND ACTIVITIES OF NUTRIENTS IN THE CELL May be involved in gene regulation or cell-signaling (pathway C) Kaput J, Physiol Genomics 2004
NUCLEAR RECEPTORS, DIETARY LIGANDS Kaput J, Physiol Genomics 2004
MICRONUTRIENT DEFICIENCY - DNA DAMAGE WITH HEALTH EFFECTS From: Kaput J: Physiol Genomics 2004 Ref 2: Ames, Toxicol Lett 1998
NUTRIGENOMICS AND NUTRIGENETICS: TWO SIDES OF A COIN • For personalized nutrition: • effects of diet on body-metabolism • influence of genotype on nutritionally related diseases • must be considered Mutch, FASEB 2005
NUTRITIONAL CONSEQUENCES OF CELLULAR PROCESS WITH GENETIC POLYMORPHISMS
NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERYTHE STEPS INVOLVED IN GENE EXPRESSION
NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERYDIET (NUTRIENTS) CAN MODULATE THESE PROCESSESFROM CELL TO POPULATION
NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERYFUNCTIONAL GENOMICS TECHNIQUES CAN ANALYZEEACH STAGE, WITH APPROPRIATE BIOMARKERS
Assesment of nutrient requirements by „omics“- based analyses Joung: J.Nutr 2001, Oliver: Nature 2000, Go: J. Nutr 2003
LC-PUFA: LONG CHAIN POLYUNSATURATED FATTYACIDS 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, • - lean and fat mass accretion, • - reproduction, • - Innate and acquired immunity, • - infectious pathologies of viruses, • - bacteria and parasites; • - the incidence and severity of virtually all • chronic • - and degenerative diseases • cancer, atherosclerosis, stroke, arthritis,diabetes, • osteoporosis, andneurodegenerative, inflammatory • and skin diseases • LC-PUFA: • Long chain polyunsaturated fatty acids • Mutch, FASEB J 2005
According to microarray studies: LC-PUFAcan mediate the functions of several transcription factors,cell-cycle regulatory genes, RNA transcription processes,prostaglandin synthesis, inducible nitric oxide synthase and related proinflammatory genes MODERN NUTRIGENOMIC TECHNOLOGIES +BIOINFORMATICS CAN TO REVEAL THE COMPLEXITY OF LC-PUFA SIGNALING
BIOLOGICAL NETWORK TRIGGERED AFTER THE CONSUMPTIONOF 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 inhibitingRNA technology, alternate analytical platforms (proteins, metabolites) etc. can clarify the biological functions,mediated by dietary lipids.