26. Etiology and pathogenesis of obesity

Direct cause of obesity?

Too large energy intake coupled with a too small energy expenditure

Real, underlying cause?

Must be endogenous

- Some endogenous need for the person to consume more food than they need

- Or: store (rather than use) more nutrients than needed

- Or: use less energy than normal

Studies on identical twins - obesity?

In twin pairs, if one twin is obese:

= There is a higher risk for the other twin to also develop obesity, compared to twin pairs where none of them are obese

If both parents are obese?

Child 10 times more likely to be obese, compared to parents where none of them are obese

Conclusion: there must be some

Genetic factors in obesity?

More likely polygenic rather than monogenic

- Some hypotheses exist as to which genetically inherited factors may be involved

Genetically inherited factors that can play a role in obesity?

- Differences in taste preferences: those who prefer more sweet food developed obesity more frequently

- Differences in palatability - the pleasure derived from certain foods

- Inherited differences in muscle structure - obese people may have more fast-twitch muscle fibers, uses less energy than slow-twitch

- Inherited disorders of chemical control of feeding behavior

- Leptin/leptin-R abnormalities

- MC4-R expression abnormalities - the receptor is stimulated by MSH and inhibited by AgRP

- POMC disorder

- PPAR-y disorders

MC4 and POMC disorders?

May explain up to 5% of morbidly obese children

- All humans with mutations in PPAR-y describes so far - have developed obesity

Leptin levels in obese people?

Leptin levels in obese people are often elevated

- May suggest that the hormone is ineffective in its normal duty in these people - just like insulin in DM2

However; recent research has cast doubt on the idea that leptin resistance causes obesity

Leptin?

A hormone produced by adipose (fat) cells that acts as a satiety factor in regulating appetite

It signals the hypothalamus and brain stem to reduce appetite and increase the amount of energy used

What does the large upswing in obesity the last 50 years indicate?

That the major cause of obesity is not genetic, but rather environmental

Whether you have genetic factors that predispose to obesity or not: keeping an adequate diet and maintain physical activity - will help you maintain a healthy body weight

What can cause "secondary" obesity?

- Insulinoma

- Cushing disease

- Hypogonadism

- Injury to the hypothalamus -> the centre of feeding behavior

- Physical inactivity due to motor disability, old age or neurological disorders

- Psychiatric diseases characterized by obsessive eating

- Depression