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Health 31 > Obesity & Inflammation > Flashcards

Obesity & Inflammation Flashcards

1
Q

what exists in overweight + obese people?

A

low grade chronic inflammation

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2
Q

What is the definition of obesity in terms of BMI?

A

BMI >30

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3
Q

What are the risk factors for obesity?

A

-Excessive food consumption

-Reduced physical activity

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4
Q

What percentage of obesity cases does genetics account for, and what is the implication of the main cause of obesity?

A
  • only <2% of cases
  • therefore most likely due to gene/environmental interactions
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5
Q

What is epigenetics?

A

study of how the environment affects which genes are expressed

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6
Q

What are the 2 types of modifications that can occur in epigenetics?

A

DNA and histone modifications… impact on RNA transcription

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7
Q

Epigenetics - Gene environment interactions leading to….

A

heritable changes in gene expression via DNA modifications

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8
Q

what DNA modifications can make a person more prone to obesity?

A

Cytosine methylations

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9
Q

What histone modifications can be made to make a person more prone to obesity?

A

Methylation/acetylation

  • histone marks which effect mRNA transcription
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10
Q

what are histones?

A

proteins that allow organisation of DNA -> chromatin

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11
Q

What are the epigenetic regulators?

A

long non-coding RNAs (>200 nucleotides)

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12
Q

How are long non-coding RNAs epigenetic regulators?

A

they act as scaffolds for the assembly of RNA transcripts and proteins

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13
Q

how are lncRNAs identified?

A

by Next Generation sequencing

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13
Q

how are lncRNAs identified?

A

by Next Generation sequencing

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14
Q

What are the 3 main causes of obesity?

A
  • genetics
  • diet
  • physical activity
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15
Q

What is metabolic syndrome? How does obesity fit into its definition?

A

at least 2 factors that -> multiple chronic diseases - 1 of these factors is obesity

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16
Q

Name the 3 factors responsible for metabolic syndrome.

A
  • insulin resistance/ hyperinsulinaemia
  • obesity (leading to) dyslipidaemia
  • hypertension
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17
Q

4 examples of chronic diseases that can be caused by metabolic syndromes?

A
  • diabetes
  • CVD
  • atherosclerosis
  • heart failure/strokes
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18
Q

obesity: associated with risk of developing….

A

OA
most px undergoing joint replacement therapy are overweight

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19
Q

particular risk factor for OA, aside from BMI?

A

WHR.
higher = apple shape = high risk
lower = pear shape = low risk

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20
Q

(summary)
effect of overeating on adipose tissue?

A

leads to pathological inflammatory adipose tissue

  • Hyperplasia of adipocytes (overgrowth of cells)
  • Increased immune cell infilitration

-> change in adipose tissue phenotype

-> secretion of cytokines (adipokines)

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21
Q

What are the functions of adipose tissue?

A
  • stores lipid
  • immunological tissue
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22
Q

What are adipokines?

A

cytokines secreted by adipose tissue

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23
Q

How does overeating affect adipocytes?

A

hyperplasia - adipocytes become bigger

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24
Q

Hyperplasia of adipocytes causes them to do what?

A
  • secrete cytokines known as adipokines
  • change their phenotype
  • both of these result in increased pro-inflammatory immune cell infiltration
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25
Q

what specific type of tissue is a major source of inflamm proteins + cytokines? where from?

A

abdominal adipose tissue from wieght gain and less exercise

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26
Q

what do adipocytes produce and how?

A

chemokines (proteins that recall immune cells into tissue)
after they accumulate lipids + get bigger and stretch

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27
Q

how does obese adipose tissue differ to lean. (BMI<25)?

A

Lean: high adiponectin
low leptin

obese: lowadiponectin
high leptin

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28
Q

what is leptin?

A

hormone that regulates food intake in body

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29
Q

resident immune cell population (for lean adipose tissue) is comprised of what and role?

A

mostly immune suppressive.
T regs/ resident macrophages… keep adipose tissue in check

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30
Q

adipose tissue acc important for what?

A

immune response

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31
Q

What causes loss of cartilage in obese people?

A

increases the release of adipokines which have a pro-inflammatory effect

32
Q

What is an issue with too many T-regs at adipose tissue?

A

At normal levels, regulate adipose tissues but too much: increase chemokines in blood -> low grade chronic inflammation

33
Q

What is adiponectin and role?

A

An adipokine secreted by adipocytes
regulates glucose levels + lipid metabolism

34
Q

What is leptin and role?

A
  • Hormone tin fat cells
  • If fat cell size increases, levels will increase
  • speeds up metabolism +inhibits appetite
35
Q

adiponectin in obese tissue: LOW, meaning?

A

ess regulation of food intake - decrease insulin sensitivity meaning increased glucose levels and metabolism

What are the levels of leptin in obese adipose tissue?
Levels of this adipokine will be high in

35
Q

adiponectin in obese tissue: LOW, meaning?

A

less regulation of food intake - decrease insulin sensitivity … increased glucose levels and metabolism

36
Q

leptin in obese tissue: HIGH, meaning?

A

metabolsim is slowed and appetite increases

They also reduce insulin sensitivity meaning increased glucose levels

37
Q

Once released, adipokines enter blood and have distal effects on (5)?
!!

A

joints, OA
skeletal muscle, sarcopenia
pancreas, diabetes
liver, steatosis
heart, CVD

-> inflammation

38
Q

What 2 additional CV risk factors do those with high WHR/central adiposity present with?

A
  • high HCL cholesterol levels
  • elevated triglycerides
39
Q

What is meant by atherogenic?

A

generates plaque in arteries

40
Q

Name five examples of adipokines

A
  • adiponectin
  • leptin
  • TNF-alpha
  • IL-6
  • PAI-1 (plasminogen activator inhibitor 1)
41
Q

What is the ‘good’ adipokine? why

A

adiponectin. only one that decreases with obesity

42
Q

What are the 3 functions of adiponectin?

A
  • Anti-atherogenic
  • Anti-inflammatory?
  • Increases insulin sensitivity
43
Q

what T2DM risk factor do those with high WHR/central adiposity present with?

A

elevated fasting glucose levels

44
Q

what are adipokines produced by (excess)??

A

obese adipose tissue

45
Q

effect of increasing adiposity/ obesity on leptin, tnfa, IL6, PAI1?

A

all increase

46
Q

What are the 2 functions of leptin?

A
  • Reduces insulin sensitivity
  • Pro-inflammatory (OA and RA joints)
47
Q

What are the 2 functions of TNF-alpha?

A
  • pro-inflammatory cytokine
  • reduces insulin sensitivity
48
Q

What are the 3 functions of IL-6?

A
  • pro-inflammatory
  • pro-atherogenic
  • increases vascular inflammation
49
Q

What are the 2 functions of PAI-1?

A
  • pro-atherogenic
  • pro-thrombotic
50
Q

What key adipokines are elevated in OA and RA synovium/serum?

A

TNF-alpha, IL-6 (OA only)

51
Q

2 things that increase risk of CHD?

A

BMI and WHR
especially both together

52
Q

relationship between age and inflammatory cytokines?

A

age increases: inflammatory cytokines increase

53
Q

Summarise how adipose tissue -> inflammation. Include: effect of over-eating, effect of adipokines, 5 key adipokines and their roles.

A

image/ drawing p70

54
Q

What is sarcopenia?

A

the age-related loss of muscle mass, strength, power and performance

55
Q

What is sarcopenia associated with?

A

age related increase in adiposity

56
Q

What does obesity lead to an accumulation of within skeletal muscle?

A

triglycerides

57
Q

How does insulin work at the cellular level?

A
  • binds to receptor
  • activates PI3K pathway
  • leads to transcription of GLUT4 transporter (into membrane)
  • GLUT4 uptakes excess glucose in blood, causing glucose in blood to go down
58
Q

How does obesity/adiposity lead to insulin resistance?

A
  • fatty acids are taken up in cell and block PI3K pathway
    …get insulin resistance
  • prevents GLUT4 transporter transcription so glucose cannot enter cell and stays in blood
59
Q

how does adiposity impact glucose levels in blood?

A

get insulin resistance
and blood glucose stays high
with increased adiposity

60
Q

impact of skeletal muscle tissue change in age + obesity on GLUT4 expression?

A

reduces expression

61
Q

obesity + skeletal muscle + insulin resistance… isolated myotubes in obesity are …

A

obese myotubes (w adiposity) = intrinsically insulin resistance

62
Q

BMI and central adiposity (WHR) impact on T2DM risk?

A

increases

63
Q

How does obesity cause skeletal muscle atrophy?

A
  • pro-inflammatory cytokines (adipokines) promote atrophy of myotubes
  • TNF-a induces muscle E3 ligases MAFbx, MURF1
64
Q

Summarise the issues obesity leads to within skeletal muscle.
(image p73)

A

…

65
Q

what do muscle cells (myoblasts) cultured in OBESE adipose media develop into?

A

thinner myotubes (muscle fibres)

66
Q

in obesity, the adipokine resistin is INC/DEC?

A

significantly increased.
if BMI >25

67
Q

myoblasts cultured in presence of adipokine resistin exhibit what?
2 specifc things?

A

impaired myogenesis
…
redcued myotube thickness
reduced nuclear fusion index

68
Q

what is myogenesis?

A

formation of skeletal muscular tissue

69
Q

obesity therapeutic: Lorcaserin is a…

A

selective serotonin 2C receptor agonist

70
Q

obesity therapeutic: Lorcaserin works on…

A

5-HT2c-R

71
Q

incWhat is the current treatment for obesity?/ adipokine modulation

A

exercise and low calorie diet

72
Q

benefits of incorporatingcombination of exercise and low calorie diet to manage obesity?

A

inc good genes e.g. adiponectin and decrease leptin, TNFa etc. :)

73
Q

key risk factor for metabolic syndrome disorders eg CVD T2DM

A

central adiposity

74
Q

pathological changes to adipose tissue in obese px ->? 2

A

infiltration of immune cells
secretion of pathological cytokines (adipokines)

75
Q

obesity + pathological adipokines are associated with… 2

A

insulni resistance and T2DM
(reduced glucose uptake and obese myotubes)

76
Q

adipokines can drive X and impair Y

A

drive muscle atrophy
impair myogenesis

77
Q

OA link with obesity occurs from…

A

obese synovial fibroblast inflamm phenotype

Health 31 (16 decks)

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