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Cancer Biology and Therapy > Obesity > Flashcards

Obesity Flashcards

(59 cards)

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1
Q

1 in __ cancers are linked to obesity

A

20

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2
Q

____% of breast cancers are caused by obesity

A

7-15

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3
Q

____% of bowel cancers are in overweight patients

A

11-14

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4
Q

risk of developing bowel cancer is ___% higher in obese men

A

50

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5
Q

TF BMI takes into consideration composition

A

no

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6
Q

healthy BMI?

A

18-25

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7
Q

overweight BMI?

A

25-29.9

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8
Q

obese BMI?

A

30-39

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9
Q

severely obese BMI?

A

> 40

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10
Q

what does visceral fat promote?

A

malignant transformation

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11
Q

how does visceral fat promote malignant transformation?

A

by producing FGF2 which binds to RTKs

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12
Q

> 10kg weight loss= ___% reduction in postmenopausal women getting BC

A

60

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13
Q

3 things obesity does to increase risk of cancer?

A

inflammation at chronic levels
oestrogen production from fat tissue
Insulin like growth factor- RTK substrate

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14
Q

in women who have diabetes and are obese, what cancer is there an increased risk of?

A

endometrial cancer

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15
Q

in women who are obese and have diabetes, what is eventually always seen?

A

hyperinsulinaemia

hyperglycaemia

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16
Q

why do these obese diabetic women have an increased risk of endometrial cancer?

A

high levels of circulating glucose which is a good energy source for rapidly proliferating tumours

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17
Q

what can oestrogen up regulate regarding glucose?

A

a group of proteins involved in glucose transport

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18
Q

___% of the population is obese or overweight

A

58

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19
Q

3 endocrine and paracrine dysregulations of adipose tissue in obesity?

A
  1. insulin- insulin high growth factor (IGF-1)
  2. sex hormone production
  3. adipocyte derived cytokines (adipokines)
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20
Q

what happens if GH secretion is suppressed and insulin secretion increases?

A

enables glucose uptake in skeletal muscle and promotes glycogenesis and adipogenesis
= obesity, ageing

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21
Q

what occurs in increased GH secretion?

A

increased physical fitness

less obesity

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22
Q

in obesity there is ______ levels of IGF. effect of this on physical fitness and leptin?

A

increased

reduces physical fitness and increases leptin

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23
Q

increased levels of leptin can lead to what?

A

leptin resistance

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24
Q

with excess body weight insulin levels ______

25
why does insulin levels increase with excess body weight?
due to GF
26
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
27
in obese people what happens to: IGFBP1 and IGFBP2? free IGF-1?
- decrease | - increase
28
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
29
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
30
free igf levels _____ with increasing body fat
increase
31
obesity ______ levels of insulin in the blood. effects?
increases | go on to trigger PI3K and RKT pathways
32
what 2 enzymes does adipose tissue produce which leads to increased oestrogen production
aromatase | hydroxysteroid dehydrogenase
33
in obesity SHBG (sex hormone binding globulin) secretion is _______. effects of this?
reduced | increased levels of available testosterone and oestrogen
34
effect of increased E2 and T on GLUT expression
increased expression
35
in pre monopausal women, adipose tissue in the periphery produces about ___% of hormones?
10
36
what happens in menopause re hormones
adipose tissue is the major driver
37
increased hormone production in post menopausal women can do what?
target breast and endometrial cells- lead to cell differentiation
38
what causes the decreased production of sex hormone binding globulin from the liver?
hyperinsulinemia- increased insulin levels cause the SHBG to reduce
39
effect of reduced SHBG in hyperinsulinemia
increase in oestrogen and T which can now diffuse to target cells and bind androgen receptors
40
what receptors do o and t bind to in target cells?
androgen
41
which enzyme can we inhibit for breast cancer treatment?
aromatase inhibitor to block oestrogen production in post menopausal women
42
3 aromatase inhibitors
anastrozole exemestane letrozole
43
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
44
what are adipokines
adipocyte derived cytokines
45
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
46
what does decreased adiponectin do?
causes insulin resistance
47
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
48
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
49
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
50
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
51
adiponectin _____ glucose uptake and ______ insulin sensitivity. what happens to it in tumours?
increases enhances it decreases in tumours
52
effect of adiponectin on fatty acids?
increases fatty acid oxidation. | fatty acids are needed for tumour metabolism
53
3 pathways in obesity associated cancers?
PI3K MAPK STAT3
54
TF a cancer associated adipocyte goes through alot of alteration?
true
55
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
56
dilapidation of adipocytes makes them acquire what type of phenotype?
a fibroblast like
57
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
58
Theres an _____ in fatty acids in cancer?
increase
59
3 main mechanisms of adipocytes enhancing cancer development? v brief pls
IGF insulin angle sex hormone angle cross talk between cytokines and tumour cells

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