Feeding

1
Feeding

• Keith Clements

2
Aims

• To discuss how the brain monitors energy
  metabolism.
• To discuss the factors which trigger and stop
  feeding.
• To consider implications for understanding and
  preventing obesity.

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Food intake and energy regulation

• Metabolic fuels
• Energy can be obtained from many nutrients
  carbohydrates, fats, proteins.
• The brain can only use glucose as fuel, the liver
  requires fats.
• Insulin
• Secreted by the pancreas after a meal
• Allows storage of glucose in muscles and liver as
  glycogen, and in fat deposits (adipose tissue).
• Allows non-brain tissues to utilise glucose.
• Between meals glucagon triggers the release of
  stored fuels.
• Weight regulation
• Both body weight and fat stores are defended.

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Obesity

• 20 over ideal body weight.
• Strong genetic contribution (70 concordance in
  MZ twins (Plomin et al.,1997).
• Risk factor for several diseases
• Increasingly seen as a chronic disorder

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Early theories

• Stellar (1954) proposed that the hypothalamus
  contained opposed satiety feeding centres.
• Damage to the Ventro-medial hypothalamus (VMH)
  triggered obesity
• Damage to the lateral hypothalamus suppressed
  eating
• But weight gain precedes eating after VMH lesions
• LH lesions have widespread effects on motivation
• Mayers Glucostatic theory
• Brain cells monitor glucose level
• In Diabetes hunger can coexist with high glucose
  levels.
• Liver glucoreceptors probably play a bigger role
  in hunger

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The onset of feeding

• Can be triggered by low blood glucose or fat.
• Campfield Smith (1990) describe transient
  decreases in blood glucose before eating. Not
  triggers for eating, but preparatory responses.
• Eating is more commonly stimulus-elicited.
• Anticipated hunger
• Variety palatability of food.

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Termination of feeding

• Many gut hormones may also act as
  neurotransmitters.
• Cholecystokinin (CCK) emulsifies fats and
  controls stomach emptying.
• Injections of CCK stop eating.
• Can induce nausea, but affects eating at lower
  doses.

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Weight regulation

• Leptin
• Identified in Ob/Ob mice
• Zhang et al. (1994) lacked gene for Leptin
• Secreted by fat cells
• Bind to receptors in hypothalamic sites
• Insulin levels also correlate with adiposity

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The hypothalamus

• Converging evidence implicates the Arcuate
  nucleus as the key centre regulating eating
  metabolism. Cells there have receptors for Leptin
  Insulin. Other peptides produced by the stomach
  (Ghrelin) intestine (PYY3-36) also convey
  information about the state of food stores.
• Release of neuropeptide Y in the nearby
  paraventricular nucleus, triggers feeding and
  reduced energy expenditure (e.g. Clark et al.,
  1984).
• Other arcuate neurons release alpha-MSH in the
  lateral hypothalmaus with opposite effects.
• Leptin has opposing effects on each population.

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Implications

• Leptin deficiency isnt a significant cause of
  obesity in humans. ?Leptin insensitivity
• Metabolic factors play a key role in weight
  regulation. The arcuate nucleus regulates both
  appetite and metabolism. Metabolic changes
  counteract the effects of dietary restriction.
• Adrenergic Serotoninergic agonists suppress
  appetite, but have been associated with adverse
  side effects. E.g. the combination of
  fenfluramine phentermine was withdrawn when it
  was found to cause heart problems. Drugs
  affecting other neurotransmitter systems are in
  development.

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References

• Chapter 4 in Wickens (2005) or chapter 12 in
  Pinel (2009).
• Woods, Schwartz, Baskin Seeley (2000). Food
  intake and the regulation of body weight. Annual
  Review of Psychology, 51, 255-277.
• International Association for the Study of
  obesity http//www.iaso.org/