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INTRODUCTION Nutrigenomics Dr. Muhamad Firdaus

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1 INTRODUCTION Nutrigenomics Dr. Muhamad Firdaus

2 Nutrigenomics. The study of how naturally occurring
Nutrigenomics 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

3 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 disease Genes alone do not necessary produce phenotypic traits Phenotypic expression is influenced by nutrition

4 Nutrition-Gene Interaction 1. Direct interactions
Nutrition-Gene Interaction 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

5 BIOLOGICAL NETWORKS Intracellular regulations Cell-cell comuniacations
Organ networks/homeostasis

6 MAIN HEALTH-RELATED CHALLENGES
Cardiovascular Cancer Diabetes-obesity Undernutrition/malnutrition Infectious diseases Allergies Ageing process

7 BIOACTIVE FOOD COMPONENTS CAN MODIFY TRANSCRIPTION, TRANSLATION AND METABOLISM

8 EFFECTS OF SELENIUM ON CERTAIN GENES
Cancer Res, 2002

9 BIOACTIVE FOOD COMPONENTS: GENETIC, EPIGENETIC AND PROTEOMIC EFFECTS
Milner J Nutr 2004

10

11 PARTIAL LIST OF BIOACTIVE FOOD COMPONENTS: WITH POSSIBLE EFFECTS ON CANCER

12 INTER-RELATIONSHIP BETWEEN BIOACTIVE FOOD COMPONENTS AND EVENTS INVOLVED IN THE CANCER PROCESS

13 FATE AND ACTIVITIES OF NUTRIENTS IN THE CELL
may act directly as ligands for transcription factor receptors (pathway A) Kaput J, Physiol Genomics 2004

14 FATE AND ACTIVITIES OF NUTRIENTS IN THE CELL
may be metabolized by metabolic pathways altering concentrations of substrates / intermediates (pathway B) Kaput J, Physiol Genomics 2004

15 FATE AND ACTIVITIES OF NUTRIENTS IN THE CELL
May be involved in gene regulation or cell-signaling (pathway C) Kaput J, Physiol Genomics 2004

16 NUCLEAR RECEPTORS, DIETARY LIGANDS
Kaput J, Physiol Genomics 2004

17 MICRONUTRIENT DEFICIENCY - DNA DAMAGE WITH HEALTH EFFECTS
From: Kaput J: Physiol Genomics Ref 2: Ames, Toxicol Lett 1998

18 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

19 Elliot, BMJ 2002

20 NUTRITIONAL CONSEQUENCES OF CELLULAR PROCESS WITH GENETIC POLYMORPHISMS

21 NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERY THE STEPS INVOLVED IN GENE EXPRESSION

22 NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERY DIET (NUTRIENTS) CAN MODULATE THESE PROCESSES FROM CELL TO POPULATION

23 NUTRITIONAL GENOMICS AND BIOMARKER DISCOVERY FUNCTIONAL GENOMICS TECHNIQUES CAN ANALYZE EACH STAGE, WITH APPROPRIATE BIOMARKERS

24 Assesment of nutrient requirements by „omics“- based
analyses Joung: J.Nutr 2001, Oliver: Nature 2000, Go: J. Nutr 2003

25 Stover: Physiol Genomics 2004

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27 LC-PUFA: LONG CHAIN POLYUNSATURATED FATTY ACIDS
A typical example of complex, bioactive molecules in nutrigenomics

28 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, and neurodegenerative, inflammatory and skin diseases LC-PUFA: Long chain polyunsaturated fatty acids Mutch, FASEB J 2005

29 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

30 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

31 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.

32 THANK YOU


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