Nutrigenomics

RNA INTERFERENCE

(RNAi). The process by which double-stranded RNA silences homologous genes.

Diet responsive v diet resistant genes

- ACSL5 gene may determine your chance of losing weight on low cal diet - variant 1 of that gene = diet resistant to low cal diet so it's hard to lose weight - 15% ppl have diet responsive - 85% have diet resistant gene

Genetic correlation btwn psychology and physiology

- BDNF = brain derived neurotrophic factor has an impact on central and sensory function - research has shown voluntary exercise inc lvls of BDNF and improves cognitive performance

2nd Strategy to Study Nutrigenomics

= strategy, which is largely theoretical at this stage, is the SYSTEMS BIOLOGY approach: gene, protein and metabolite signatures that are associated with specific nutrients, or nutritional regimes, are catalogued, and might provide 'early warning' molecular biomarkers for nutrient-induced changes to homeostasis. - the second strategy might be more important for human nutrition, given the difficulty of collecting tissue samples from 'healthy' individuals.

1st Strategy of Studying Nutrigenomics

= traditional hypothesis-driven approach: specific genes and proteins, the expression of which is influenced by nutrients are identified using genomics tools — such as transcriptomics, proteomics and metabolomics — which subsequently allows the regulatory pathways through which diet influences homeostasis to be identified - Transgenic mouse models and cellular models are essential tools in this approach, which can allow new genes and pathways to be identified -In future, such models might provide the key to understanding the interactions between metabolic and INFLAMMATORY signalling routes -The first strategy will provide us with detailed molecular data on the interaction between nutrition and the genome, whereas

How many adults are obese?

> 1/3

LASER CAPTURE MICRODISSECTION

A method in which cells are cut out from a tissue sample using a laser beam, allowing single cell expression analysis.

TRANSDOMINANT NEGATIVE ADENOVIRAL CONSTRUCT

A recombinant adenovirus that infects cells, resulting in the high-level expression of a mutant protein that, for example, specifically blocks a given signalling pathway (superrepressor) by competing with the endogenous protein.

PHARMACOGENOMICS

A term often used to mean the influence of DNA- sequence variation — in drug targets, Phase I or Phase II drug-metabolizing enzymes, and transporters — on the effect of a drug, which ultimately allows physicians to design individualized therapy.

Personalized Diets

- SNPs should provide powerful molecular tools for investigating the role of nutrition in human health and disease. - Incorporating studies of SNPs into metabolic and epidemiological studies might also help to define optimal diets. - The combination of twin studies with advanced genetic analysis might allow us to understand the basis of complex traits and the impact of sensitizing genotypes on the development of polygenic diet-related diseases such as diabetes. - In future, this might lead to the adjustment of dietary recommendations on the basis of genotype - Although the implementation of this type of personalized diet its still in its infancy, progress in the next few years is likely to be rapid.

Nutrigenomics summary

- nutrient sensors (transcription) - Nutrigenomics testing (preventative measure) - Nutrigenomics (genetics of nutrients) - nutrigenetics (your genetic variation) - possible public health interventions: genetically tailored program for diet, fitness and exercise to motivation to more ex and mot

What can we do about obesity?

- personalized prevention and treatment - Nutrigenomics - public health

FTO Gene (fat mass and obesity associated gene)

- regulates amt of fat our bodies store by controlling appetite - variants in this gene cause ppl to feel hungry even if you've eaten enough leading to inc consumption - indiv with this variant also eats food that contain more calories

Limitations if Nutrigenomics

-Food is complex mixture of nutrients - Most nutrients are weak dietary sig- nals and must be considered in the context of chronic exposure. - It has to be shown that nutrigenomics offers the tools to measure such weak dietary signals, or is able to detect modest nutritional deficiency in humans. - researchers also must deal with the challenge of understanding polygenic diet- related diseases. -we must be prepared to address genome-scale questions rather than limited specific hypothesis, to gain the highest profit from this wealth of data. -the expense of such research is another important barrier to be overcome before nutrigenomics reaches its full potential.

Gene expression profiling purposes

1. Nutrient sensors that lead to beneficial or adversary mechanism 2. Molecular biomarkers that can be used as "predisease" phase 3. Nutrient impact on basic pathway and regulation

What percent of diet is junk food?

29%

What percent chronic diseases associated with obesity ?

60% and is responsible for 20% rise in HC costs in last 2 decades

Nutrigenetics

= examines the effect of genetic variation on the interaction between diet and disease or on nutrient requirements. - Genetics has a pivotal role in determining an individual's risk of developing a certain disease -Population differences in single nucleotide polymorphisms (SNPs) can have an important effect on disease risk.

Nutrigenomics

= focused on the effect of nutrients on the genome, proteome and metabolome -the application of high- throughput genomics tools in nutrition research - it will promote inc understanding of how nutrition influences metabolic pathways and homeostatic control, how this regulation is disturbed in the early phase of a diet-related disease and to what extent individual sensitizing genotypes contribute to such diseases. - will allow effective dietary-intervention strategies to recover normal homeostasis and to prevent diet-related diseases.

MICRONUTRIENTS

Dietary compounds, including vitamins and minerals that are required in small amounts in the diet.

How have obesity rates grown?

Doubled for adults and tripled for kids

DTC test

GAO investigated saying they predicted medically unproven diseases ? Bye

Limitations to personalized diet

However, if the use of genotypes in the dietary prevention of disease is to be estab- lished, the field of molecular nutrition must first be successful in identifying the mecha- nisms driving the connection between diet and phenotype according to specific genetic variations. Understanding how nutrient- sensing transcription factors mediate the effects of dietary components on gene expression (see above) will be crucial if this endeavour is to succeed.

PROTEOMICS

The study of proteomes (the complete collection of proteins in a cell or tissue at a given time), which attempts to determine their role inside cells and the molecules with which they interact.

NUTRIGENOMICS

The study of the genome-wide influences of nutrition or dietary components on the transcriptome, proteome and metabolome, of cells, tissues or organisms, at a given time.

METABOLOMICS

The study of the metabolome, which is the entire metabolic content of a cell or organism, at a given time.

MACRONUTRIENTS

Organic compounds, including proteins, amino acids, carbohydrates and lipids, that are required in large amounts in the diet.

SYSTEMS BIOLOGY

The study of whole biological systems (cells, tissues and organisms) using holistic methods.

SATURATION

The binding state of a C-C bond in a fatty acid molecule.

TRANSCRIPTOME

The complete collection of gene transcripts in a cell or a tissue at a given time.

INFLAMMATION

The complex series of reactions that occur in the host as a response to injury, trauma or infection of a tissue, which prevent ongoing tissue damage, isolate and destroy the infective organism and activate the repair processes that are necessary to return the organism to normal function.

ACUTE-PHASE RESPONSE

The early and immediate set of homeostatic control reactions that are induced during inflammation

KETOGENESIS

The production of ketone bodies — such as acetoacetate and β-hydroxybutyrate — which are the intermediate products of fatty-acid catabolism and can be used to provide energy.

NUTRIGENETICS

The relationship between genotype and the risk of developing diet-related diseases, such as cancer, diabetes type II and cardio-vascular diseases