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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
fats include cholesterol and triglycerides - where are they stored
adipose tissue
26
protein in food is needed for making proteins. it is broken down. what disease occurs if there is failure to break down proteins
BSE
27
how are fats broken down in the body
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
28
any excess glucose is stored as glycogen. storage and release are regulated by
insulin and glucose
29
what does insulin do
reduced blood sugar by increasing glycogen synthesis and slowing glycogen breakdown
30
exess sugars are converted to fats via what enzyme
acetyl CoA
31
some tissues can only use glucose eg
red blood cells
32
skeletal muscle can use glucose or free fatty acids or ketone bodies
T
33
in starvation fat can be converted into ketone bodies which can keep most processed going except which tissue
the brain
34
GWAS has shown a strong association of obesity with a range of genes T/F
T
35
what is the heritability of obesity
70%
36
there is evidence that obesity is programmed early T/F
T
37
what is a microbiome and how does this affect obesity
population of microbes. genetically identical rats fed to develop different microbiomes. when switched to identical diets obesity and microbiome exists
38
obese people can have a different microbiome which means that they...
extract more energy from food
39
obesity is sometimes descirbed as a metabolic syndrome. why?
there are a lot of things going wrong at the same time
40
there is a strong link between obesity and what
diabetes
41
the adipose tissue is not just a fat store it is also a
endocrine organ (secretes signals/hormones)
42
adipose tissue releases inflammatory mediators that are generically called
adipokines
43
what do adipokines released by the adipose tissue promote
infiltration of immune cells (macrophages) into adipose tissue, which can start a vicious circle of inflammation
44
what chronic inflammation signal do adipose tissues also release
TNF-alpha | increases release of free fatty acids from adipocytes
45
what do adipose tissue increase the production of which may further the risk of atherosclerosis
reactive oxygen species
46
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
T
47
not all adipose tissue is the same which is the one that causes the most health problems and why
``` visceral fat (around the abdomen) generates more adipokines ```
48
what does white adipose tissue store
energy in fat
49
brown adipose tissue contains lots of mitochondria. what is its function
burns fats to regulate thermogenesis
50
which type of adipose tissue is healthier
brown because it takes fat from white adipose tissue and burns it
51
brown adipose tissue activity is stimulated by sirtuin what does this do
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
what are sirtuins thought to be important for
positive correlation between low calorie intake and longevity
53
what does a deficiency in leptin lead to
overeating
54
what does leptin regulate
appetite
55
what other functions does leptin have
increase in fatty acid oxidation, increase in insulin sensitivity and increased energy expenditure
56
adipose tissue contains leptin meaning that it works in a negative feedback mechanism
increases adipose tissue reduces fat accumulation
57
what gene is linked to the most common single gene form of obesitym
MC4R
58
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
FTO
59
FTO accounts for ..% of the heritability of obesity
1%
60
what does FTO stimulate
the development of white adipose tissue rather than beige (makes up brown)
61
FTO deficiency protects against obesity but this is not a good basis for a drug -w why
loss-of-function change in FTO has severe developmental problems
62
the ER has elaborate mechansm for dealing with unfolded proteins. this can be referred to
unfolded protein responsee
63
what does the unfolded protein response (UPR) consist of
halt protein translation degrade unfolded proteins by proteosome induce expression of chaperones
64
what happens if the unfolded protein response doesnt work
cell induces apoptosis
65
what causes ER stress which then leads to the unfolded protein response
high levels of circulating fatty acids caused by chronic high calorific intake
66
UPR is useful as a short term response but what does it lead to when permenantly over-activated
inflammation and insulin resistance
67
what is the est way of reducing obesity
reducing calorie intake plus exercise
68
what is the major drug for obesity
Xenical - inhibits pancreatic lipase and so reduces fat absorption

Biochem basis of human disease (6 decks)

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