Cardiophysiology: Pathogenesis of Obesity Flashcards
What happens to adipocytes when they experience excessive growth?
Apoptosis and necrosis which leads to inflammation.
What are leptin’s functions?
Reduces appetite (binds to neurons in the brain)
Affects milk production
Affects fetal growth
Why do fat cunts still eat so much with so much fat?
Obese people develop leptin resistance.
What happens to leptin levels during cardiac failure and ischaemia?
they rise independently of obesity
What is the other effect that leptin has on the brain?
Acts on the ventromedium hypothalamus which acts on the sympathetic nervous system.
What effect does increased leptin have on sympathetic activity and how does it do this?
The ventromedium hypothalamus does not lose sensitivity as quickly as the neurons in the brain responsible for appetite do.. As a result sympathetic activity increases
What happens to lean animals when acutely given leptin?
Increased natriuresis
Increased NO production
Decrease in Na+ transporter expression and as a result less Na+ retention
What happens in animals with chronic hyperleptinaemia?
Increase in sodium retention.
NO deficiency
Increase in renal oxidative stress
What is TNF-alpha?
Pro inflammatory cytokine produced by immunocytes
What is TNF-alpha produced in response to?
Leptin
What cells produce TNF-alpha?
monocytes and macrophages
What does weight loss do to TNF-alpha levels?
It drops TNF-alpha levels which decreases insulin resistance.
What is the function of TNF-alpha?
Pro inflammatory
Correlated with insulin resistance
What effect does increased TNF-alpha have in obese people?
An increase in TNF-alpha causes people to develop metabolic conditions more often
What conditions result from too much TNF-alpha?
TNF-alpha is associated with increase in acute and chronic ischaemia and heart failure.
TNF-alpha induces migration, inflammation, and apoptosis of smooth muscle and this is associated with vascular degeneration.
Adhesion molecule formation
How does TNF-alpha cause vascular degeneration?
TNF-alpha induces migration, inflammation, and apoptosis of smooth muscle
What is adiponectin?
Anti-inflammatory adipokine that is reduced in obese individuals and higher in lean individuals.
What is low adiponectin a marker of?
Type 2 diabeetus
Left ventricular hypertrophy
myocardial infarction
coronary artery disease
How is adiponectin reduced?
It is reduced in obese individuals by leptin and tnf-alpha expression
What does adiponectin do?
Reduces inflammation
exerts protective effects on endothelial cells and cardiomyocytes
What happened to knock out mice after they were given adiponectin?
Revascularization of ischaemic limbs
Reduced cerebral reperfusion injuries
What happens to blood pressure in adiponectin deficient mice?
Salt-sensitive hypertension develops.
Nitric Oxide production is reduced resulting in less vasodilation and in turn higher blood pressure
What effect does adiponectin have on atherosclerosis?
overexpression inhibits in lesion formation
Deficiency augments atherosclerosis
What happens to insulin resistance with high adiponectin levels?
it is reduced
Why are scientists so focused on adipokines?
Adipokines are associated with the development
of numerous obesity-related illnesses
What weight loss is considered successful?
success if you loose 10% initial body weight and don’t regain more
than 3 kg in 2 years
What conditions result from obesity during pregnancy in the fetus?
pre-eclampsia
gestational diabetes
gestational hypertension
DVT in mother
What are the odds of keeping weight off after losing it after being overweight?
1/210 for men
1/124 for women
What are the odds of keeping weight off after losing it after being severely obese?
1/290 for men
1/677 for women
What happens to offspring if mother is overweight?
Maternal obesity programs metabolic dysfunction in offspring
Maternal obesity increased risk of congenital heart defects in children
In rats maternal obesity,
persistent hypertension
Basal renal SNS activity
What tissue produce leptin?
the placenta, the GIT mucosa, and the mammary gland.
What is growth restriction in utero?
What are the causes of growth restriction in utero?
Uteroplacental insufficiency (Western world)
Maternal undernutrition (Third world)
What happens to offspring that are growth restricted during adulthood?
Decrease in nephron number at birth
Decrease in cardiomyocyte number
Hypertension
Decrease in beta cell number
Glucose tolerance
Increase in amount of visceral and abdominal fat
What is transgenerational programming?
Disease outcomes are exacerbated when mother or father were obese prior to conception of the fetus.
What are second-hits?
Disease outcomes in individuals born small are exacerbated by other lifestyle factors
What are some examples of second-hits?
Diet
Age
Lifestyle
Pregnancy
Being male (science is sexist >.>)
What effect did exercise during pregnancy have?
Exercise reduces the effect of a high fat diet and decreased dorsal fat, glucose intolerance.
No changes in plasma leptin were observed
