Lecture 17 - Obesity and Metabolic Syndrome

What cells make up adipose tissue?

adipocytes

Where can adipose tissue be found in the body?

many locations, including around visceral organs

Adipocytes are used to store?

TAG (triacylglycerol)

Adipocytes are integral in maintaining what?

- lipid homeostasis

- energetic metabolism

Energy homeostasis

Balance of energy intake (food) and expenditure.

Things that contribute to energy intake

- Fats

- Proteins

- Carbohydrates

Things that contribute to energy expenditure

- Basal metabolic rate (BMR)

- Physical activity

- Thermic effect of food

What percent of total energy expenditure is due to BMR?

55-60%

Does BMR change?

No, it's relatively stable once we enter adulthood.

It increases as children and decreases after 60 years

What percent of total energy expenditure is due to physical activity?

20-30%

What percent of total energy expenditure is due to thermic effect of food?

10-15%

Thermic effect of food

the energy necessary to process, digest, absorb and store nutrients in the body

Can the thermic effect of food vary?

Yes, it depends on our diet

Carbs are easier to breakdown than fat and proteins

Which energy expenditure factor is the most variable?

Physical activity

- how much we move is up to us

What happens when we chronically experience an energetic disequilibrium? (We eat more than we use)

Obesity

Obesity definition

BMI of 30 or higher

Types of obesity

- Visceral fat

- Subcutaneous fat

What type of obesity increases the risk of many other diseases?

Visceral fat obesity

Obesity increases the risk of developing which diseases?

- Cardiovascular disease (heart attack, stroke)

- Type II Diabetes

- Cancer

Visceral fat obesity

Excess fat accumulation around the visceral organs

Gender difference in fat storage

For the benefit of pregnancy women store fat more subcutaneously

Men more viscerally

Which type of fat is more difficult to access and why?

Visceral fat because it's an abnormal way to store fat

Ways the body accommodates fat

adipocyte hyperplasia and hypertrophy

Hyperplasia

increase in number of cells

Hypertrophy

increase in cell size

Both subcutaneous and visceral adipose tissues (SAT and VAT) expand through...

hyperplasia and hypertrophy

Which way is the better way to accommodate fat? and why?

Hyperplasia has a protective effect against obesity-associated metabolic complications

- all the signalling pathways of the cell are intact

Adipogenesis

generation of new adipocytes

Ectopic fat storage

Storage of fat in odd places ex: muscle

Why do we see ectopic fat storage in unhealthy obesity?

hyperplasia of SAT adipocytes reaches its limit, excess fat is redistributed to more a harmful adipose tissue depot

Lipotoxicity

adverse effects of fat in nonadipose tissues (ectopic)

Symptoms of lipotoxicity

hypoxia, low grade inflammation, insulin resistance

Healthy expansion

- ↑ adipogenesis

- ↓ cell volume

- ↑ insulin sensitivity

- ↓ inflammation

Unhealthy expansion

- ↓ adipogenesis

- ↑ cell hypertrophy

- ↓ insulin sensitivity

- ↑ low-grade inflammation

- ↑ macrophge infiltration

Adipose tissue can be considered an...?

active endocrine organ

Adipokines

protein hormones made and released by adipose tissue (fat) cells

Other than adipocytes, what type of cell can make adipokines?

resident macrophages

Hypoxia theory

As the adipose tissue mass expands (obesity), groups of adipocytes will become more and more distant to blood vessels.

Under hypoxic conditions, adipose tissue changes its expression of adipokines

Changes to adipokine secretion in adipose tissue under hypoxic conditions

- increased HIF-1α

Overexpression of HIF1α leads to what changes in adipokine secretion?

- increased leptin

- increased TNF1α

- increased IL-6

- decreased adiponectin

Normoxia

normal levels of oxygen (21%)

HIF-1α (hypoxia inducible factor-1α)

a transcription factor that regulates the expression of ~1300 genes

overexpressed in obese mice

What happens to HIF1α in normoxic conditions?

it is degraded

HIF1α and Cancer

Under hypoxic conditions HIF1a is not degraded and it continues to promote the transcription of many genes.

Can lead to cancer because it leads to increased vascularization (angiogenesis) and metabolism in these cells

What is a summary of the changes in adipokine secretion due to obesity?

we see an increase in the expression of unwanted adipokines and a decreases in expression of protective adipokines