Health benefits Flashcards
What are the latest recommendations for exercise?
30 minutes moderate intensity at least 5 days a week
150 minutes
Why is PA regarded as a bigger risk factor to health than smoking?
65% males and 76% females do not achieve the weekly guidelines for exercise
When is the build up of fatty plaque first present in life?
1st decade of life
When is cholesterol dangerous?
When it has been modified, e.g. oxidised
What protein wraps around LDL and HDL?
Apolipoprotein
A - HDL
B - LDL
What initiates plaque formation?
Damage/infection to endothelial layer
Why is there more adhesion molecules at the branch points of the arteries?
Less laminar flow
Less flow over eNOS
Less production of nitric oxide
Reduced vasodilation and increased adhesion molecules
What is the role of apolipoproteins?
To interact with other tissues
A - liver
B - less specific
Fatty plaque formation and atherosclerosis
Damage/infection to endothelial layer
WBC release cytokines attracting monocytes
Monocytes interact with adhesion molecules
Enter endothelial layer via diapedesis
PLGF promotes smooth muscle in intima
Monocytes mature into macrophages
Consume modified cholesterol forming foam cells
Macrophages release proteolytic enzymes and free radicals
Enhancing necrotic core
Leading to further inflammation
What happens if cholesterol levels drop?
Cells produce more LDL receptors
LDL binds to receptor
Cell cholesterol level increases
Why do macrophages consume cholesterol in an uncontrolled way
Scavenger receptors on membrane identifies pathogen - modified LDL
Scavenger cells can not turn off
What makes HDL an atherogenic? (3)
Slows the modification of cholesterol
Reduces expression of adhesion molecules
Promotes cholesterol efflux
What is cholesterol efflux?
Free cholesterol taken up by HDL
Binds by LCAT enzyme
Transported to liver and binds via apolipoprotein A
Excreted as bile
What are the benefits of exercise on HDL levels?
TG in circulation for a shorter period
Why does it take longer for fats to appear in the bloodstream?
Fats packaged into chylomicrons in intestine
Assembled in lacteals and drained from lymphatic system
Chylomicron broken down and enters liver - monoglycerol and FFA
Apolipoprotein B100 repackages fat into VLDL
What happens when VLDL ‘bumps’ into LDL/HDL?
Exchange of TAG and CE
Via CEPT
HDL catabolised in kidney
What are the effects of TG rich VLDL on lipoprotein profile?
VLDL increases
HDL decrease
What test can we do to measure fat levels?
Oral fat tolerance test
What happens to fat during exercise? (2)
LPL break down FFA and enters muscle
Liver oxidises more fat, less being repackaged into VLDL
What effect does prior exercise have on blood flow?
Blood flow is redistributed towards the liver
What is a benefit of regular exercise training on fat?
Increased LPL due to capillarisation
Decreasing LDL and VLDL
What enzymes breakdown/reform fat stores?
LPL
HSL
What is insulins effect on fat storage enzymes?
LPL - activates
HSL - inhibits
What action does insulin have on the hepatocytes?
Inhibits apoB100, therefore decreasing repacking into VLDL
What effect does training have on LCAT and CEPT?
LCAT increases
CEPT decreases
What are the best methods to assess body composition?
MRI
DEXA
Underwater weighin
How many years does obesity reduce lifespan by?
Approx. 8-10 years
What are increased disease risks associated with obesity?
CVD
Hypertension
Stroke
Cancer
Diabetes
Does fat or CHO have a larger store of energy in adipose tissue?
Fat
Fat 9kcal/g, CHO 4kcal/g
What proteins does adipose tissue produce? (4)
Adipokine
Leptin
Adiponectin
aP2
What cytokines does adipose tissue produce?
TNF-a
Il-6
What happens in the proximal insulin cascade?
Insulin binds to receptor
Tyrosine exposed becoming phosphorylated
IRS-1 binds to beta unit becoming phosphorylated
Activates PI3 kinase
Phosphorylating PIP2 to PIP3
What effect does fat derivatives and TNF-a have on the insulin cascade pathway?
Exposure of serine inhibits phosphorylation of IRS-1
What effect does obesity have on insulin and fat storage?
Decreased activation of LPL
Decreased inhibition of HSL
What is the role of adipokines - which one is the odd one out?
Make cells insulin resistance
Adiponectin is insulin sensitive
What effect does obesity have on adipokines?
Increases insulin resistance
Decreases insulin sensitivity
What molecule inhibits the action of CPT-1 and therefore the oxidation of fat in the mitochondria?
Malonyl-coA
Describe the pathway that inhibits the action of malonyl-coA on CPT-1?
Adiponection binds to receptor
Phosphorylating AMPK
Phosphorylating ACC
Inhibits conversion of acetyl-coA
Preventing fat accumulation
What effect does training have on adipokines?
Insulin resistance adipokines decrease
Adiponectin increases
What components contribute to energy expenditure?
Exercise
Non-exercise activity (NEAT)
Thermal effect of feeding (TEF)
Basal metabolic rate (BMR)
What is BMR?
The amount of energy required by the body when lying down - largest contributor to energy expenditure
What happens to energy balance when exercise intensity increases?
Overall greater negative energy balance
Increase in energy consumption
What happens to BMR if undertaking a diet?
Decrease in fat AND muscle
Decreasing BMR
What hormone is responsible for regulation metabolic rate?
T3 - produced in the thyroid
Name the hunger hormones and their functions. (2)
Ghrelin - increases drive to eat
Leptin - decreased drive to eat
What is the effect of obesity on ghrelin?
Increased drive to eat
What is the effect of obesity on leptin?
The brain desensitises activity of leptin
Therefore, ghrelin not switched off
Leading to insulin resistance
What hormone release glucose into the bloodstream?
Glucagon
What methods are used to measure insulin sensitivity/resistance?
Hyperinsulinemia euglycemic clamp
Oral glucose tolerance test
HOMA
Describe the process of the hyperinsulinemia euglycemic clamp protocol
Flood the body with large amount of insulin
Translocation of GLUT4
Measure through back of hand
Glucose infusion altered to steady state
When is the golden period to consume CHO?
Within 30 minutes post exercise as GLUT4 transporters are still present on membrane
What activates AMPK enzyme?
AMP
Calcium
What drug can be given to replicate AMP and ‘trick’ to activate AMPK?
AICAR drug - phosphorylated to become ZMP
Describe the distal insulin cascade pathway.
PKB phosphorylates TBC1D4
Conversion of Rab-GPD to Rab-GTP
GLUT4 translocated to membrane
Describe the insulin-independent cascade pathway.
AMP and calcium increase
Activating AMPK
Phosphorylating TBC1D4
Converting Rab-GDP to Rab-GTP
Translocation of GLUT4
What drug can be given to reduce the risk of type 2 diabetes?
Metformin
How does regular training promote mitochondrial biogenesis?
Increase AMP and calcium
Activates AMPK
Activating transcription factor
Enters nucleus and attaches to PGC1-a
How does training alter glycaemic control?
Expression of GLUT4
Production of GLU4
Insulin signalling
Increase glycogen synthase
What are the 4 actions of AMPK?
GLUT4 translocation
GLUT4 production
Fat transport into mitochondria
Mitochondrial biogenesis
What does Syndrome X relate to?
The resistance to insulin-stimulated uptake of glucose
What is the action of insulin on ghrelin?
Decreases release of ghrelin
What is de novo lipogenesis?
Conversion of glucose into TG
What are thiazolidinediones?
Family of drugs that correct insulin resistance - pioglitazone
What is the action of thiazolidinediones?
Activates PPAR-g to store TG in adipose
Increases adiponectin
How does insulin vasodilate blood vessels?
Insulin binds to receptor
IRS-1 activates IP3K
Activates eNOS
Increased release of nitric oxide
Vessel dilates
Why is PAI-1 more active in obese people?
Blood is more likely to clot, therefore PAI-1 required
