C2 Pathogenesis of obesity and interventions to prevent progression

Question 1

Obesity

Answer 1

• Classified as low-grade inflammation
• BMI >30
• Independent risk factor for co-morbidities
• ↑in adipose tissues

Question 2

Adipocytes

Answer 2

• What makes up adipose tissues
• Secretes:
  
  • Cytokines
  • Chemokines
  • Hormone-like factors

Question 3

Adipokines

Answer 3

• Pro-inflam adipose-derived cytokines
• Linked to the pathogenesis of obesity

Question 4

Consequences of incresed caloric intake

Answer 4

• ↑caloric intake → ↑adipocyte hyperplasia
• Response blunted with age → leading to adipocyte hypertrophy

Question 5

Advanced obesity

Answer 5

• Adipocytes undergo necrosis/apoptosis → recruit inflammation cells & causes adipocyte dysfunction

Question 6

Leptin

Answer 6

• A pro-inflammatory adipokine (16kDa - small)
• Physiological plasma conc = 59.5ng/ml
• Secreted by adipose tissues (& also by placenta/mammary)
• May play a role in fetal growth restriction
• Responsible for maintenance of hunger & satiety
  
  • ↓hunger, ↑energy expenditure → ↑weight loss

Question 7

Obesity and leptin

Answer 7

• x5 [leptin] in obesity
• Obesity is characterised by leptin resistance/sensitivity state
  
  • Effect in basomedial hypothalamus diminished

Question 8

Leptin on CVD

Answer 8

• ↑ after myocardial infarction
• ↑ in patients with heart failure regardless of BMI

Question 9

Leptin on immune cells

Answer 9

• Acts on immune cells to ↑cytokines

Question 10

Leptin on ANS

Answer 10

• Activates SNS (↑NA & A)

Question 11

Kidney’s role in CVD

Answer 11

• Renal denervation in obesity cauese ↓hypertension
• Have different response to leptin (depending on acute/chronic interaction)

Question 12

Leptin’s effect on kidneys

Answer 12

• Acute leptin exposure ↓ hypertension by:
  
  • ↑natriuresis
  • ↑NO (vasodilator)
  • ↓renal Enac
• Chronic hyperleptinemia:
  
  • ↑Na rentention
    
    • NO deficiency → ↑renal oxidative stress
    • ↑Na ENaC

Question 13

TNFa

Answer 13

• Pro inflammatory adipokine
• Prod. By macrophage & monocytes

Question 14

TNFa and obesity

Answer 14

• Obesity → ↑TNFa in plasma & adipocytes
• TNFa Correlates with insulin resistance
  
  • In obesity, inhibiting TNFa → ↑insulin signalling

Question 15

TNFa and CVD

Answer 15

• ↑ in chronic ischemia injuries & heart failure
• ↑ gene expression → develops atherosclerosis
  
  • Pro-inflammatory
  • Pro-coagulant
  • Proliferative
• Induces apoptosis in SM → associated withn vascular pathologies

Question 16

Adiponectin

Answer 16

• Anti-inflammatory adipokine, prod. by adipocytes
• ↓in obesity (inhibited by pro-inflammatory cytokines)
• Protective action on CV cells

Question 17

Function of adiponectin

Answer 17

• Improves insulin resistance (Muscles)
• Inhibits atherosclerosis (Artery)
• Improves angiogenesis and endothelial dysfunction (Capillary)
• Improves pathological hypertrophy and ischemic injury (Heart)

Question 18

Adiponectin as a predictor of type II diabetes

Answer 18

• Adiponectin deficiency → ↑insulin resistance
• Adiponectin treatment → improves metabolic parameters

Question 19

Adiponectin and CVD

Answer 19

• ↓serum adiponectin:
  
  • ↑coronary A diseases
  • Hypertension
  • CV hypertrophy
  • ↑ risk of MI
• Develop salt-sensitive hypertension
  
  • ↓NO synthase activity
• Overexpression inhibits atherosclerotic lesion formation

Question 20

Treatment/prevention of obesity

Answer 20

• Lifestyle, medicine
• Weight-loss surgery:
  
  • Gastric binding/bypass → all ↓stomach size/digestion
• Successful treatment = losing 10% bodyweight & don’t’ regain >3kg in 2 years

Question 21

Maternal obesity

Answer 21

• ↑Cytokine production (placenta also prod. cytokines)
• ↑Risk of pre-eclampsia, gestational diabetes, hypertension
• Fetal programming of metabolic dysfunction and CVD

Question 22

Exericse’s effect on diabete

Answer 22

• ↓gestational diabetes in animals & humans (some other studies in humans found no link)