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Molecular Basis of Disease > Obesity, insulin resistance and inflammation > Flashcards

Obesity, insulin resistance and inflammation Flashcards

1
Q

What is the diagnostic cutoff for obesity?

A

> 30

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2
Q

Which conditions are linked with obesity?

A

CVD

Diabetes

Hypertension

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3
Q

What percentage of children were obese in 2016?

A

16%

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4
Q

In which class was the rate of childhood obesity the lowest?

A

Households with the highest incomes

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5
Q

What is important regarding the effect of adipose tissue on health?

A

The location of the adipose tissue

3 sites: perivascular, subcutaneous, omental

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6
Q

What happens to cytokine levels in obesity?

A

They are chronically in high levels

Lower than during true inflammation, but considered potential contributors to obesity complications

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7
Q

What are the physiological roles of adipose tissue?

A

Cushioning

Thermal insulation

Energy storage

Normal glucose homeostasis

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8
Q

How do we know adipose tissue is involved in normal glucose homeostasis?

A

Transgenic mice with no AT are markedly diabetic

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9
Q

What are adipokines?

A

Signals released by adipose tissue

Can be autocrine, paracrine or endocrine

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10
Q

What is the effect of adipokines?

A

Enable changes to fuel metabolism

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11
Q

What is adipose tissue composed of?

A

Different cell types

Adipocytes count for at least 50% of the tissue

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12
Q

What did Dr Friedman discover?

A

Leptin/leptin receptor deficient mice are morbidly obese

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13
Q

What is the effect of leptin?

A

Has a feedback effect on the hypothalamic energy regulation

Involved in muscle fat oxidation and insulin resistance

Congenital leptin deficiencies make sufferers constantly craving food

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14
Q

Which gene codes for leptin?

A

OB gene

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15
Q

How is obesity and leptin related?

A

Obesity is a leptin-resistant state

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16
Q

How many signals are involved in the adipose tissue as an endocrine organ?

A

120 signals

17
Q

Classes of signals involves in adipose tissue

A

Cytokine-like molecules

Chemokines

Acute Phase Proteins

Others

18
Q

Examples of cytokine-like molecules released by adipose tissue

A

Leptin

Adiponectin

IL-6

TNF-a

IL-10

Lipocalin

19
Q

Examples of chemokines released by adipose tissue

A

MCP-1

RANTES

20
Q

Examples of Acute Phase Proteins released by adipose tissue

A

Serum amyloid A

C-reactive protein

PAI-1

VEGF

21
Q

Other molecules released by adipose tissue

A

NO

COX pathway components

MicroRNAs

22
Q

What have the signals released from adipose tissue been linked to?

A

Vascular tone control

Atherosclerosis

CV risk factors

23
Q

Link between IL-6 and obesity

A

Levels decrease with increased weight

24
Q

What is adiponectin linked with?

A

C1q

25
Q

What happens to adiponectin in obesity?

A

Reduced in obesity

26
Q

How is adiponectin linked to insulin?

A

The higher the level of adiponectin, the more sensitive to insulin

27
Q

What happens to adiopnectin upon endothelial injury?

A

Accumulates in vascular walls in response to endothelial injury

28
Q

Desribe the protective effect of adiponectin

A

Inhibition of mature macrophage function

Inhibition of TNF-a induced release of adhesion molecules

Modulation of endothelial inflammatory response

Vasodilator - eNOS

29
Q

What does normal fat induce?

A

Protection from cardiovascular disease

Through release of anti-inflammatory cytokines

30
Q

What does dysfunctional fat induce?

A

Cardiovascular disease

From release of pro-inflammatory adipokines

31
Q

How is normal and dysfunctional fat different?

A

In normal fat, all the cells have good circulation and are vascularised well

Every adipocyte has nerve and vessel proximity

In dysfunctional fat there is infiltration of fat into the area

More lipid-enlarged and atrophied

Focal point for infiltration of macrophages

32
Q

Describe the interactions between epicardial adipokines and vessel wall

A

The molecular mechanisms are not completely known

33
Q

How do adipokines travel to the site they are needed?

A

Epicardial adipokines can reach inner vascular layers via diffusion or via vasorum

34
Q

What is the concentration of adiponectin in epicardial fat in response to injury?

A

Lower than normal

Perivascular injury causes the leakage of adipokines as a result of plaque rupture

35
Q

Effects of adipokines on vessel wall

A

Systemic adipokines are mostly detrimental

Adiponectin in anti-inflammatory and anti-atherogenic

The significance of others is unclear

36
Q

What do adipokines represent?

A

A metabolic repertoire enabling the organism to make adaptive changes to fuel metabolism

37
Q

Importance of the adipose tissue endocrine organ

A

Malfunction could be linked with obesity

Molecular Basis of Disease (28 decks)

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