Nutrigenetics midterm

epigenetics

chromatin modifications that don’t involve genome sequence changes

characteristics of euchromatin

open, less densely packed, easily accessible to transcription factors, loose nucleosome arrangement

characteristics of heterochromatin

closed, compact, functionally repressed state, not easily accessible to transcription factors

What is the purpose of chromatin remodeling and alterations in nucleosome structure?

to increase or decrease gene expression of particular genes by controlling the accessibility of genomic binding sites for transcription factors

Mechanisms by which chromatin are remodeled and nucleosome structure is altered

* Lys, Arg, Ser residues are subject to post-translational, covalent, reversible modifications: acetylation, methylation, and phosphorylation
* carried out by enzymes like HATs, HDACs, HMTs, and HDMs

HATs

histone acetyltransferases; enzymes that acetylate histones (increase gene expression)

HDACs

histone deacetylases; enzymes that remove acetyl groups from histones (could either increase or decrease gene expression, but mostly repression- depends on the exact residue)

HMTs

histone methyltransferases; methylate histones

HDMs

histone demethyltransferases; demethylate histones

effect of DNA methylation on gene expression

represses gene expression

intermediary metabolism

the process by which signals from the environment, as well as nutrients taken into the body, are metabolized, resulting in signal transduction pathways that activate gene expression programs that integrate signals originating from the environment

examples of molecules in the connections between products of intermediary metabolism and chromatin modifiers

* chromatin modifiers: HATs, HDACs, KAT3/2B, BRDs, DNMTs, etc.
* signaling molecules: SAM, FAD, NAD, acetyl-CoA, ATP, etc.

writer enzymes

add on chemical groups

* HATs, DNMTs, KMTs

reader enzymes

start cascade of events caused by change from writers

eraser enzymes

take modifications away

What is the role of a methyl group donor molecule in gene expression regulation?

makes sure there are methyl groups there to be used for methylation- decrease gene exp.

2 examples of methyl group donors and their roles

SAM- s-adenosyl-methionine: donates methyl groups to DNA in conjunction with DNMT (DNA methyltransferase)

How do methyl group donors support a link between intermediary metabolism and proper gene expression regulation?

* once DNA is methylated, recruitment of HDAC, methyl binding proteins, and co-repressors occurs

gene transcription off

concentrations of NAD+/NADH, acetyl-CoA/CoA, and AMP/ATP in a high nutritional state

high NADH, high acetyl-CoA, high ATP, also high SAM

concentrations of NAD+/NADH, acetyl-CoA/CoA, and AMP/ATP in a low nutritional state

low NADH and high NAD, low acetyl-CoA and high CoA, low ATP and high AMP, also low SAM and high SAH

effect of ATP concentrations in low nutritional state

* AMP/ATP ratio controls AMPK activity
* In a low nutrient state, AMP concentrations rise because cells consume more ATP than they produce, so they are under energetic stress
* AMP binds the gamma subunit of AMPK heterotrimer and activates the kinase, leading to phosphorylation of histones (histones are AMPK substrates)

effect of ATP concentrations in high nutritional state

no AMPK activity, modified histone phosphorylation pattern, different set of gene activity

effect of acetyl-CoA in high nutritional state

HAT stimulation, leading to histone acetylation

effect of acetyl-CoA concentrations in low nutritional state

higher CoA concentrations block HATs

effect of NADH concentrations in high nutritional state (clarify)

high NADH

effect of NADH concentrations in low nutrient state

NAD+ stimulates sirtuins leading to histone deacetylation

SAM concentrations in high nutritional state

high SAM activates KMTs, leading to histone methylation

SAM concentrations in low nutritional state

low SAM and high SAH; SAH inhibits DNMTs leading to inhibition of histone methylation

Mediterranean diet characteristics

* more omega-3s
* olive oil
* fruit
* vegetables
* fish

Nordic diet characteristics

* plant foods, less meat
* associated with lower risk of chronic conditions like heart disease, stroke, T2D, cancer, lower inflammation
* canola oil
* more omega-6s

What is the main difference between the Mediterranean and Nordic diets?

* Mediterranean diet favors olive oil, and the Nordic diet favors canola oil
* both have high omega-3 fatty acids, but canola oil has more omega-6s than omega-3s

A high omega-6 to omega-3 ratio can cause _______ while a high omega-3 to omega-6 ratio can _______

inflammation; reduce inflammation

There is daily communication between ___ and _____, including gene regulatory networks in:

* diet and genome
* metabolic organs
* immune system
* brain

metabolic organs

skeletal muscle, adipose tissue, pancreas and liver, immune system and brain

homeostasis means that each cell has the correct ____ of ______

the correct concentration of necessary molecules

What controls processes to maintain homeostasis?

* gene networks
* the molecular and cellular processes controlled by these networks maintain homeostasis and prevent onset of non-communicable diseases

How does obesity establishment occur?

broken energy homeostasis + inefficient regulation

characteristics of obesity

* blunted mechanisms controlling energy balance
* modified perception of energy control signals
* new body weight reference
* modified gastrointestinal hormone levels
* insulin and leptin resistance
* resistance to weight loss
* development of other pathologies/conditions

nutrigenomics is the influence of ____ on ______ and provides a genetic understanding for:

influence of nutrients on gene expression

* provides genetic understanding for how common dietary components affect the balance between health and disease by altering the expression and/or structure of an individual’s genetic makeup

nutrigenetics is the ________ of _________ on

heterogenous response of gene variants to nutrients, dietary components, and developing nutraceuticals

nutrigenetics is also the _______ that impacts the body’s responses to __________ by influencing their

the genetic profile that impacts the body’s responses to bioactive food components by influencing their absorption, metabolism, and site of action

nutrigenetics is how our ______ affects how we ___________

how our DNA sequence affects how we utilize our nutrients

bioactive compounds

molecules that can affect the body, whether good/bad, healthy/unhealthy

SNPs

Single Nucleotide Polymorphism- a change in a single nucleotide

significance of SNPs for nutrition and disease prevention

Genetic variation is known to affect food tolerances among human subpopulations and may also influence dietary requirements and raising the possibility of individualizing nutritional intake for optimal health and disease prevention on the basis of an individual’s genome

epigenetic modifications

changing gene expression without altering DNA sequence

examples of epigenetic modifications

* DNA methylation
* structural changes to histones
* miRNA

Effect of DNA methylation on gene expression

inhibits expression

Effect of histone structural changes on gene expression

affects accessibility of DNA, which alters expression depending on whether or not TFs and RNA pol II can get in for transcription

miRNA effect on gene expression

binds to mRNA and signals for mRNA degradation- inhibits expression

Epigenetic changes can affect __________

the next generation

* prenatal exposure to certain dietary compounds and/or malnutrition or overnutrition impacts offspring

300,000 to 10,000 years ago, humans were _______

hunters/gatherers

Effect of the agricultural revolution on human nutrition

* use of domesticated animals and plants started 10,000 yrs ago
* shifted diet to higher rates of starch
* intro of sugar
* salt for conservation

Result: reduced nutritional diversity, since starch alone already represented more than 60% daily caloric intake

Effect of the industrial revolution on human nutrition

* less physical activity
* increased use of refined food, such as grains and oils
* diet lower in starch and fiber but higher in white sugar and fat
* HIGHER energy density and glycemic load

Modern nutrition

* industrially processed dietary products and fast food
* very high sugar and fat content = high energy density but low fiber content
* MORE reduced physical activity

All of this leads to a POSITIVE ENERGY BALANCE

What is a positive energy balance?

a surplus of energy

* higher glycemic load and energy density because of lower starch and fiber content paired with higher white sugar and fat content
* more processed foods, fast food, less activity also play a role

How does height indicate public health?

* ancestors of 30,000 yrs resembled us, but Roman soldiers, middle age peasants much shorter
* dropped height average indicates worse nutrition and more infection
* recovery observed in rich nations in 20th/21st centuries

Energy flipping point

a surplus of energy from nutrition that we then need to store

cause for increase in daily caloric intake from 1909 to 2000

revolution in the food industry- food preservation, packaging, less time in the kitchen

two principles of metabolism

catabolism (breaking down) and anabolism (building)

catabolism

macronutrients provide the body with energy when they are metabolized

anabolism

precursor molecules are used to synthesize new macronutrients

main macromolecules in diet

carbohydrates, fats (lipids), proteins

main micronutrients

vitamins and minerals

How are the macro and micronutrients regulated in the body?

* macronutrients provide body with energy when they are metabolized
* excess of energy-rich nutrients stored in form of glycogen in liver and skeletal muscle or triacylglycerols in adipose tissue
* used in anabolism for synthesis of new macronutrients
* enzyme cascades; many require micronutrients as co-enzymes

glucose is the and is absorbed during

most common dietary monosaccharide; absorbed directly into bloodstream during digestion of polysaccharides and disaccharides

3 forms of dietary carbs

* polysaccharides (starch)
* disaccharides (sucrose, lactose)
* monosaccharides (glucose, fructose)

purpose of glucose for CNS and RBCs

CNS largely reliant on glucose as metabolic fuel and RBCs are even entirely dependent on it

function of insulin

nutrients and metabolites regulated the expression of genes that make products functioning in these metabolic pathways either directly or indirectly

What is the major cause of metabolic syndrome?

disturbances in insulin signaling

What happens when blood glucose levels increase?

* promotes insulin release from the pancreas
* insulin travels to the liver, where it stimulates the formation of glycogen
* insulin also stimulates glucose uptake from the blood

Effect: blood sugar (glucose) is lowered

What happens when blood glucose levels are low?

* glucagon release promoted from the pancreas
* stimulates breakdown of glycogen to glucose
* glucose released from the liver, therefore raising blood glucose levels

role of the liver in metabolism

* energy storage of carbohydrates
* metabolize AAs and fatty acids

adipose tissue role in metabolism

* stores most of the body’s energy as triacylglycerols
* releases fatty acids in lipolysis when other tissues need energy

purpose of fat in metabolism

* stores energy (most efficient)

How many essential AAs in diet? Are they stored for energy?

9; not stored for energy

What are AAs required for?

* protein synthesis
* nucleic acid synthesis

(basic cell functions)

3 branched chain AAs and their function

* leucine
* isoleucine
* valine
* muscle recovery

Why would proteins be broken down?

during stress to get carbon for synthesis of other molecules like glucose

3 types of dietary fats

* triacyl glycerols (triglycerides)- dietary fat molecule building blocks
* cholesterol
* phospholipids

4 roles of dietary fats

* energy via FA B-oxidation
* cofactors for enzymes
* biologically active molecules - signaling/gene expression regulation
* cell membranes - cells to stay intact

types of biologically active molecules

* steroid hormones
* eicosanoids (prostaglandins)

4 types of fatty acids

* saturated- no double bonds, animals
* trans - artificial, one or more double bonds
* monounsaturated - one cis double bond, plants
* polyunsaturated - multiple cis double bonds, plants

What is common in chronic metabolic diseases?

disturbances in lipid metabolism (dyslipidemias)

How are trans fats made and where can they be found?

when food makers turn liquid oils into solid fats, like shortening or margarine- found in fried, fast, packaged foods

___ of NCDs are ________ and a common cause of them is , which leads to

* 70-90% are preventable
* common cause of NCDs is obesity
* leads to 5-20 years decreased life expectancy for the individual

DALY

disability adjusted life years- measures the disease or disability burden in populations

* combining measures of life expectancy as well as the adjusted quality of life during a disease or disability for a population

= YLL (years of life lost) + YLD (years lived with disability)

QALY

quality adjusted life years

individual measure of the benefit with and without medical intervention

5 risk factors of noncommunicable diseases

* genetic factors
* environmental factors
* sociodemographic factors
* factors of self-management
* factors of medical conditions

list of lifestyle factors that can contribute to obesity and OCD

* fiber
* high intake of processed foods that are energy dense but micronutrient poor
* soda (lots of sugar) and fruit juices

list of lifestyle factors that can increase the risk of CVD

* myristic and palmitic acids
* trans fatty acids
* high sodium intake
* overweight
* high alcohol intake

4 levels of evidence

convincing, probable, possible, insufficient

pseudoscience

picking and choosing studies and evidence that backs your claim- built on confirmation bias

When does cancer occur?

when normal control of cell division is lost

What can influence cancer development?

dietary molecules

* primary tumors vs. metastatic cancer

mutational theory of cancer

DNA mutations cause cancer

process of cancer developement

* 1 cell has a gene mutation
* hyperplasia- that cell replicates abnormally
* carcinoma in situ - compromising function of tissue
* invasive cancer - metastasis

driver vs. passenger mutations

* driver: cause development of the cancer
* passenger: part of tumor but not really the cause

see slide 14 ch. 1

How can we explain the existence of cancer without mutation and mutation without cancer?

* genes may carry the potential to cause cancer, but epigenetic and metabolic conditions determine the expression of that gene into a cancerous mutation
* the metabolic condition may determine the state of epigenetic conditions, which in turn dictate how genes are expressed
* migration and twin studies support that environment and lifestyle changes can cause cancer rather than an individual’s genome

What is part of the cause for both cancer and obesity?

inflammation