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Biochem basis of human disease > williamson - obesity > Flashcards

williamson - obesity Flashcards

1
Q

what different process occur in inflammation

A

increased blood flow
accumulation of leukocytes in damaged tissue
increased permeability of endothelial cells lining the blood vessels

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2
Q

what are the 3 general effects of inflammation

A
  • vasodilatin
  • oedema (swelling)
  • erythema (tissue goes red)
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3
Q

the locally created signal to stimulate both the oedema and the vasodilation comes from…

A

prostaglandins

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4
Q

prostaglandins can be autocrine and can be paracrine. they cant be endocrine - why?

A

they do not originate from endocrine glands but from a wide range of cells

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5
Q

how are prostaglandins produced

A

through the oxidation of fatty acids (usually arachidonic acid) by an enzyme called cyclooxygenase (COX)

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6
Q

arachidonic acid is converted into prostaglandin H2 what is this then converted into

A

thromboxane and prostacyclin

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7
Q

thromboxane and prostacyclin have opposite effects T/F

A

T

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8
Q

what does prostacyclin do

A

it is a vasodilator. inhibit the aggrefgation of platelets. it stimulate inflammation and migration of leukocytes into the tissue

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9
Q

what do thromboxanes do

A

they are vasoconstrictors and promote platelet aggregation

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10
Q

inhibition of prostacyclin will prevent vasodilation and reduce inflammation

A

T

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11
Q

in blood clotting - damaged tissue leads to activation of platelets. the activated platelets stick to the damaged tissue to form a plug. they also release various signals one of which is ……… which further activated other platelets

A

thromboxane

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12
Q

the damaged tissue causes changes to proteins circulating in blood, which ultimately activates prothrombin to thrombrin and fibrinogen to fibrin. normally this is inhibited by …

A

prostacyclin

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13
Q

drugs that inhibit COX are anti-inflammatories and form the group of…

A

NSAID (non steroidal anti-inflammatories)

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14
Q

what is a famous example of a NSAID

A

aspirin

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15
Q

how does aspirin work

A

inhibits COX by irreversibly acetylating it. reduction of thrombane synthesis reduces clotting and hence it is used in low doses to reduce risk of heart attack

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16
Q

what is an example of a newer NSAID

A

ibuprofen

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17
Q

how does paracetemol work

A

inhibits COX2

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18
Q

why is COX-2 a good target

A

mainly found in inflamed tissues so an inhibitor would reduce inflammation but not cause gastric irratation

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19
Q

COX2 is more important in making

A

prostacyclins but less important for thromboxanees

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20
Q

if you inhibit COX2 that is important in synthesis of prostacyclin but not really thromboxane what effect may you get

A

reduced inflammation (less prostacyclin) but increase the risk of thrombosis (doesnt affect production of thromboxanes)

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21
Q

vioxx was a COX-2 inhibitor but what were the problems

A

shown an increased risk of heart attack with higher doses

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22
Q

what is obesity

A

consequence of consuming more energy intake than your body needs

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23
Q

what is the typical energy daily need of an adult

A

2500kcal male - 2000kcal female

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24
Q

what is the average daily intake in the UK

A

3400kcal

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25
Q

fats include cholesterol and triglycerides - where are they stored

A

adipose tissue

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26
Q

protein in food is needed for making proteins. it is broken down. what disease occurs if there is failure to break down proteins

A

BSE

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27
Q

how are fats broken down in the body

A

triaglycerides are emulsified by bile salts, broken down by lipase then reassembled into triaglycerides and packaged into alipoprotein bound chlomicrons.
lipids pass into lymph system and then into blood

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28
Q

any excess glucose is stored as glycogen. storage and release are regulated by

A

insulin and glucose

29
Q

what does insulin do

A

reduced blood sugar by increasing glycogen synthesis and slowing glycogen breakdown

30
Q

exess sugars are converted to fats via what enzyme

A

acetyl CoA

31
Q

some tissues can only use glucose eg

A

red blood cells

32
Q

skeletal muscle can use glucose or free fatty acids or ketone bodies

A

T

33
Q

in starvation fat can be converted into ketone bodies which can keep most processed going except which tissue

A

the brain

34
Q

GWAS has shown a strong association of obesity with a range of genes T/F

A

T

35
Q

what is the heritability of obesity

A

70%

36
Q

there is evidence that obesity is programmed early T/F

A

T

37
Q

what is a microbiome and how does this affect obesity

A

population of microbes.
genetically identical rats fed to develop different microbiomes. when switched to identical diets obesity and microbiome exists

38
Q

obese people can have a different microbiome which means that they…

A

extract more energy from food

39
Q

obesity is sometimes descirbed as a metabolic syndrome. why?

A

there are a lot of things going wrong at the same time

40
Q

there is a strong link between obesity and what

A

diabetes

41
Q

the adipose tissue is not just a fat store it is also a

A

endocrine organ (secretes signals/hormones)

42
Q

adipose tissue releases inflammatory mediators that are generically called

A

adipokines

43
Q

what do adipokines released by the adipose tissue promote

A

infiltration of immune cells (macrophages) into adipose tissue, which can start a vicious circle of inflammation

44
Q

what chronic inflammation signal do adipose tissues also release

A

TNF-alpha

increases release of free fatty acids from adipocytes

45
Q

what do adipose tissue increase the production of which may further the risk of atherosclerosis

A

reactive oxygen species

46
Q

regulation of the immune system gets worse with age so chronic inflammation arising from obesity is likely to have more serious consequences as you age

A

T

47
Q

not all adipose tissue is the same which is the one that causes the most health problems and why

A 
visceral fat (around the abdomen)
generates more adipokines
48
Q

what does white adipose tissue store

A

energy in fat

49
Q

brown adipose tissue contains lots of mitochondria. what is its function

A

burns fats to regulate thermogenesis

50
Q

which type of adipose tissue is healthier

A

brown because it takes fat from white adipose tissue and burns it

51
Q

brown adipose tissue activity is stimulated by sirtuin what does this do

A

it is a deacetylase - removes acetyl groups on histones and thereby changes gene regulation. thought to be involved in response to starvation - upregulate in low energy intake

52
Q

what are sirtuins thought to be important for

A

positive correlation between low calorie intake and longevity

53
Q

what does a deficiency in leptin lead to

A

overeating

54
Q

what does leptin regulate

A

appetite

55
Q

what other functions does leptin have

A

increase in fatty acid oxidation, increase in insulin sensitivity and increased energy expenditure

56
Q

adipose tissue contains leptin meaning that it works in a negative feedback mechanism

A

increases adipose tissue reduces fat accumulation

57
Q

what gene is linked to the most common single gene form of obesitym

A

MC4R

58
Q

The first gene identified by GWAS and the largest single gene associated with BMI is an alpha-ketoglutarate-dependent dioxygenase that catalyses demethylation of mRNA. what is it calledd

A

FTO

59
Q

FTO accounts for ..% of the heritability of obesity

A

1%

60
Q

what does FTO stimulate

A

the development of white adipose tissue rather than beige (makes up brown)

61
Q

FTO deficiency protects against obesity but this is not a good basis for a drug -w why

A

loss-of-function change in FTO has severe developmental problems

62
Q

the ER has elaborate mechansm for dealing with unfolded proteins. this can be referred to

A

unfolded protein responsee

63
Q

what does the unfolded protein response (UPR) consist of

A

halt protein translation
degrade unfolded proteins by proteosome
induce expression of chaperones

64
Q

what happens if the unfolded protein response doesnt work

A

cell induces apoptosis

65
Q

what causes ER stress which then leads to the unfolded protein response

A

high levels of circulating fatty acids caused by chronic high calorific intake

66
Q

UPR is useful as a short term response but what does it lead to when permenantly over-activated

A

inflammation and insulin resistance

67
Q

what is the est way of reducing obesity

A

reducing calorie intake plus exercise

68
Q

what is the major drug for obesity

A

Xenical - inhibits pancreatic lipase and so reduces fat absorption

Biochem basis of human disease (6 decks)

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