Obesity, insulin resistance and inflammation Flashcards
What is the diagnostic cutoff for obesity?
> 30
Which conditions are linked with obesity?
CVD
Diabetes
Hypertension
What percentage of children were obese in 2016?
16%
In which class was the rate of childhood obesity the lowest?
Households with the highest incomes
What is important regarding the effect of adipose tissue on health?
The location of the adipose tissue
3 sites: perivascular, subcutaneous, omental
What happens to cytokine levels in obesity?
They are chronically in high levels
Lower than during true inflammation, but considered potential contributors to obesity complications
What are the physiological roles of adipose tissue?
Cushioning
Thermal insulation
Energy storage
Normal glucose homeostasis
How do we know adipose tissue is involved in normal glucose homeostasis?
Transgenic mice with no AT are markedly diabetic
What are adipokines?
Signals released by adipose tissue
Can be autocrine, paracrine or endocrine
What is the effect of adipokines?
Enable changes to fuel metabolism
What is adipose tissue composed of?
Different cell types
Adipocytes count for at least 50% of the tissue
What did Dr Friedman discover?
Leptin/leptin receptor deficient mice are morbidly obese
What is the effect of leptin?
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
Which gene codes for leptin?
OB gene
How is obesity and leptin related?
Obesity is a leptin-resistant state
How many signals are involved in the adipose tissue as an endocrine organ?
120 signals
Classes of signals involves in adipose tissue
Cytokine-like molecules
Chemokines
Acute Phase Proteins
Others
Examples of cytokine-like molecules released by adipose tissue
Leptin
Adiponectin
IL-6
TNF-a
IL-10
Lipocalin
Examples of chemokines released by adipose tissue
MCP-1
RANTES
Examples of Acute Phase Proteins released by adipose tissue
Serum amyloid A
C-reactive protein
PAI-1
VEGF
Other molecules released by adipose tissue
NO
COX pathway components
MicroRNAs
What have the signals released from adipose tissue been linked to?
Vascular tone control
Atherosclerosis
CV risk factors
Link between IL-6 and obesity
Levels decrease with increased weight
What is adiponectin linked with?
C1q
What happens to adiponectin in obesity?
Reduced in obesity
How is adiponectin linked to insulin?
The higher the level of adiponectin, the more sensitive to insulin
What happens to adiopnectin upon endothelial injury?
Accumulates in vascular walls in response to endothelial injury
Desribe the protective effect of adiponectin
Inhibition of mature macrophage function
Inhibition of TNF-a induced release of adhesion molecules
Modulation of endothelial inflammatory response
Vasodilator - eNOS
What does normal fat induce?
Protection from cardiovascular disease
Through release of anti-inflammatory cytokines
What does dysfunctional fat induce?
Cardiovascular disease
From release of pro-inflammatory adipokines
How is normal and dysfunctional fat different?
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
Describe the interactions between epicardial adipokines and vessel wall
The molecular mechanisms are not completely known
How do adipokines travel to the site they are needed?
Epicardial adipokines can reach inner vascular layers via diffusion or via vasorum
What is the concentration of adiponectin in epicardial fat in response to injury?
Lower than normal
Perivascular injury causes the leakage of adipokines as a result of plaque rupture
Effects of adipokines on vessel wall
Systemic adipokines are mostly detrimental
Adiponectin in anti-inflammatory and anti-atherogenic
The significance of others is unclear
What do adipokines represent?
A metabolic repertoire enabling the organism to make adaptive changes to fuel metabolism
Importance of the adipose tissue endocrine organ
Malfunction could be linked with obesity