Hunger

[Ref: WG22:p235-240]

Feeding centre vs satiety centre

Hypothalamus regulates appetitde by interaction of 2 areas:

1. Feeding centre
   * Lateral, in the bed nucleus of the medial forebrain bundle
2. Satiety centre
   * Medial, in the ventromedial nucleus

NB:

• Feeding centre is chronically active
• Satiety centre transiently inhibits feeding centre activity

 

Factors that increase food intake

• Ghrelin
• Neuropeptide Y
• Orexin-A and orexin-B
• Melanin-concentrating hormone (MCH)

Factors that decrease food intake

• Pro-opiomelanocortin (POMC)
• Leptin
• Malonyl-CoA
• Glucagon
• Somatostatin
• Oxytocin
• CRH

Afferent mechanisms

4 hypothesis, not mutually exclusive

• Lipostatic hypothesis
  * Adipose tissues produces humoral signal proportional to its fat store
  * The signal reduces food intake and increase energy consumption
• Gut peptide hypothesis
  * Food in GIT causes release of polypeptides that inhibits food intake
  * e.g. ghrelin, GRP, glucagon, somatostatin, cholecystokinin
• Glucostatic hypothesis
  * Increase glucose utilisation in the hypothalamus produce satiety
• Thermostatic hypothesis
  * Fall in body temperature stimulate appetite
  * Rise in body temperature inhibits appetite

1. Lipostatic hypothesis

Leptin

• Product of ob gene
• Produced primarily in fat cells
• A circulating protein containing 167 amino acids

Function

• Acts on hypothalamus to decrease food intake and increase energy consumption
• Appears to decrease activity of neuropetide Y neurons and increase activity of POMC-secreting neurons
• Appears to cause bone loss
  --> Significance uncertain

Leptin receptor

db gene is responsible for production of leptin receptor

Receptor has different form

The significant form is mostly found in the arcuate nuclei

Also found in brown adipose tissue
--> Leptin may also increase the heat-producing activities of brown adipose tissue

Conclusion

• In human, obesity is more likely to be due to leptin receptor defect than leptin defect
• Effect of leptin appears relatively prolonged.
• Meal-to-meal control may be due to gut peptides

2. Gut peptide hypothesis

Ghrelin

• 28 amino acid polypeptide
• Opposite to leptin in action
• Produced in stomach
  --> Production reduced when food is eaten
• Stimulates arcuate nucleus

Function

• Stimulates growth hormone secretion
• Stimulates food intake

Conclusion

• Significance yet to be determined

3. Glucostatic hypothesis

Glucose

Activity of satiety centre in the ventromedial nuclei
--> At least partly dependent on glucose utilisation by the neurons in it

When glucose utilisation by these neurons is low
--> Decreased activity
--> Hunger

When glucose utilisation is high
--> Increased activity
--> Sated

Thus,

• Hypoglycemia stimulates appetitde
• DM causes low cellular utilization of glucose
  --> Polyphagia

4. Temperature

Cold temperature --> Increased food intake

Warm temperature --> Decreased food intake

But,
Temperature is unlikely to play a role in regulation

Others

Social, environmental, cultural factors all play a role