Obesity Flashcards
1 in __ cancers are linked to obesity
20
____% of breast cancers are caused by obesity
7-15
____% of bowel cancers are in overweight patients
11-14
risk of developing bowel cancer is ___% higher in obese men
50
TF BMI takes into consideration composition
no
healthy BMI?
18-25
overweight BMI?
25-29.9
obese BMI?
30-39
severely obese BMI?
> 40
what does visceral fat promote?
malignant transformation
how does visceral fat promote malignant transformation?
by producing FGF2 which binds to RTKs
> 10kg weight loss= ___% reduction in postmenopausal women getting BC
60
3 things obesity does to increase risk of cancer?
inflammation at chronic levels
oestrogen production from fat tissue
Insulin like growth factor- RTK substrate
in women who have diabetes and are obese, what cancer is there an increased risk of?
endometrial cancer
in women who are obese and have diabetes, what is eventually always seen?
hyperinsulinaemia
hyperglycaemia
why do these obese diabetic women have an increased risk of endometrial cancer?
high levels of circulating glucose which is a good energy source for rapidly proliferating tumours
what can oestrogen up regulate regarding glucose?
a group of proteins involved in glucose transport
___% of the population is obese or overweight
58
3 endocrine and paracrine dysregulations of adipose tissue in obesity?
- insulin- insulin high growth factor (IGF-1)
- sex hormone production
- adipocyte derived cytokines (adipokines)
what happens if GH secretion is suppressed and insulin secretion increases?
enables glucose uptake in skeletal muscle and promotes glycogenesis and adipogenesis
= obesity, ageing
what occurs in increased GH secretion?
increased physical fitness
less obesity
in obesity there is ______ levels of IGF. effect of this on physical fitness and leptin?
increased
reduces physical fitness and increases leptin
increased levels of leptin can lead to what?
leptin resistance
with excess body weight insulin levels ______
increase
why does insulin levels increase with excess body weight?
due to GF
direct inhibitory effects of growth hormone on insulin signalling does what? re lipolysis and hepatic glucose output
reduce insulin sensitivity and this increases the lipolysis and increases hepatic glucose output
in obese people what happens to:
IGFBP1 and IGFBP2?
free IGF-1?
- decrease
- increase
why does reduced levels of IGFBP-1 and 2 result in increased levels of IGF1?
this happens when there’s an ______ in body weight
as they bind IGF1 so if they decrease then there’s an increase in free IGF-1 levels in the plasma
what is the effect of the increase in free IGF1 and what effect does this have on cancer cells?
IGF1 is a substrate to RTK igf1 receptor which can lead to tumour development
free igf levels _____ with increasing body fat
increase
obesity ______ levels of insulin in the blood. effects?
increases
go on to trigger PI3K and RKT pathways
what 2 enzymes does adipose tissue produce which leads to increased oestrogen production
aromatase
hydroxysteroid dehydrogenase
in obesity SHBG (sex hormone binding globulin) secretion is _______. effects of this?
reduced
increased levels of available testosterone and oestrogen
effect of increased E2 and T on GLUT expression
increased expression
in pre monopausal women, adipose tissue in the periphery produces about ___% of hormones?
10
what happens in menopause re hormones
adipose tissue is the major driver
increased hormone production in post menopausal women can do what?
target breast and endometrial cells- lead to cell differentiation
what causes the decreased production of sex hormone binding globulin from the liver?
hyperinsulinemia- increased insulin levels cause the SHBG to reduce
effect of reduced SHBG in hyperinsulinemia
increase in oestrogen and T which can now diffuse to target cells and bind androgen receptors
what receptors do o and t bind to in target cells?
androgen
which enzyme can we inhibit for breast cancer treatment?
aromatase inhibitor to block oestrogen production in post menopausal women
3 aromatase inhibitors
anastrozole
exemestane
letrozole
why are the aromatase inhibitors not used in pre menopausal breast cancer?
as aromatase isn’t the key producer of sex hormones in these women
what are adipokines
adipocyte derived cytokines
Adipose tissue dysfunction leading to insulin resistance, type 2 diabetes and chronic inflammation is caused by combination of what 3 things?
________ adipokine production
________inflammatory cytokine production
_______ adiponectin production
increased adipokine production
increased inflammatory cytokine production
decreased adiponectin production
what does decreased adiponectin do?
causes insulin resistance
what happens to the size of adipocytes in obesity? what do they produce?
enlarge
chemotactic factors e.g. MCP-1 which attracts monocytes and macrophages to adipose tissue which then cause inflammation and insulin resistance
example of a chemotaxis factor which adipocytes release in obesity- what does it do?
MCP-1
which attracts monocytes and macrophages to adipose tissue which then cause inflammation and insulin resistance
dur to with increased adipokines and inflam cytokines and the decrease in adiponectin, what happens to fatty acids? what does this lead to?
adipose tissue loses its ability to store fatty acids
insulin resistance and chronic inflammation
what is leptin? what does it regulate?
EFFECT ON APPETITE?
an adipocyte specific hormone
regulates food intake and body weight in the cns
DECREASES appetite
adiponectin _____ glucose uptake and ______ insulin sensitivity.
what happens to it in tumours?
increases
enhances
it decreases in tumours
effect of adiponectin on fatty acids?
increases fatty acid oxidation.
fatty acids are needed for tumour metabolism
3 pathways in obesity associated cancers?
PI3K
MAPK
STAT3
TF a cancer associated adipocyte goes through alot of alteration?
true
3 ways cancer associated adipocytes undergo alteration?
delipidation= fibroblast type phenotype
loss of terminal diffrenciation marker expression e.g. adiponectin and FA binding proteins (due to pro inflammatory cytokines e.g. IL6
LIPOLYSIS CAUSES THEM TO RELEASE FATTY ACIDS
dilapidation of adipocytes makes them acquire what type of phenotype?
a fibroblast like
what differentiation markers have decreased expression when an adipocyte is being transformed in cancer? what is this caused by?
adiponectin
FA binding protein
caused by pro inflammatory cytokines e.g. IL6
Theres an _____ in fatty acids in cancer?
increase
3 main mechanisms of adipocytes enhancing cancer development? v brief pls
IGF insulin angle
sex hormone angle
cross talk between cytokines and tumour cells