Appetite Regulation

Caloric Homeostasis
1. Prandial (absorptive) state
  1. Recently fed, lots of free energy sources. Precursors anabolised (glucose to glycogen, fatty acids to triglycerides) for energy stores
  2. High levels of insulin allows the cells to use glucose from the blood as an energy source, promoting the storage of glucose as glycogen
2. Post-absorptive state
  1. Between meals, reduced free energy sources. Storage molecules catabolised into precursors for energy sources for cells
  2. Insulin levels have fallen, signalling the catabolism of stored energy sources.
3. Insulin is important in this process and it is released in three phases
  1. Cephalic
    1. Anticipation, smell and taste of food activates the neural pathway to the β cells of the pancreas. Insulin then signals the decrease in catabolism of stored energy sources, preparing the body for food
  2. Gastro-intestinal
    1. When food enters the GI tract, hormones are released, releasing more insulin
  3. Substrate
    1. Absorbed nutrients induce more insulin release, so levels remain high after feeding
Plasma Osmolality
1. An increase in the plasma concentrate of electrolytes such as Na+ and Cl- inhibits feeding, as well as increasing thirst
2. Feeding is reduced when water is withheld (dehydration anorexia) or is accompanied with a hypertonic fluid.
  1. Effect is mediated by osmoreceptors in the brainstem
Satiety Signals
1. Physical and chemical signals affecting the regulation of short and long term feeding behaviour
2. Gastric distension
  1. Activation of stretch receptors after feeding as stomach volume increases
    1. Signals the sensation of feeling full
    2. Decreases feeding, although this reflex can be overidden
3. Cholecystokinin (CKK)
  1. Secreted into the stomach to aid digestion and absorption
    1. Binds to receptors on the vagus nerve, aiding the inhibitory effects of gastric distension on appetite
  2. Can be blocked by receptor antagonists and lesions to the nucleus of solitary tract (NTS), which is where the impulses are received
Adiposity
1. Body fat levels affect feeding behaviour
  1. Food deprivation with weight loss leads to increased feeding until the level of adiposity is restored
  2. Forced feeding with weight gain leads to decreased feeding until adiposity has returned to normal levels
  3. Parabionts
    1. Two animals surgically joined by skin or muscle with the same circulation but individual nervous systems
      1. Joining a lean and obese animal causes the lean animal to lose weight, suggesting that factors released by the obese animal cause a decreased food intake and increased satiety in the lean animal
        Proof that fat deposits communicate with the brain by releasing chemical mediators into the circulation
  4. Leptin
    1. Hormone secreted into the blood by adipose tissue
    2. Levels in the plasma are directly proportional to adiposity
      1. Negative feedback for caloric homeostasis
    3. Mutations
      1. Receptor
        Hyperphagia and obesity
        Leptin administration does not cure as the receptor is inactivated
        Ob-R, cytokine receptor found in hypothalamus. Carry out intracellular signalling via the Jak/Stat pathway
      2. Gene
        Hyperphagia and obesity
        Leptin administration cures
2. Mutations in the insulin receptor gene increases feeding and causes obesity
  1. Human obesity is linked to leptin and insulin resistances
Dual Centre Hypothesis
1. Ventromedial Nuclei (VMN)
  1. Satiety centre
  2. Lesions induce hyperphagia and obesity
    1. Also causes autonomic dysfunction, increased insulin resistance and eating more often
    2. New feeding set point is established and eating stops when the new increased weight is reached
2. Lateral Hypothalamus (LH)
  1. Hunger centre
  2. Lesions induce aphagia and starvation
    1. Also causes adipsia, akinesia and sensory neglect
Neuropeptides
1. Lateral Nucleus (LH)
  1. Appetite stimulation
  2. AgRP
    1. Released from arcuate nucleus, enhances appetite by acting as an MC4 receptor antagonist, blocking the effects of α-MSH
      1. Prevents a decrease in orexin A release from the LH, as well as preventing the increase of CRH release in the PVN.
    2. Long lasting effects
  3. NPY
    1. Released from the arcuate nucleus and enhances appetite by acting on NPY receptors (Y1 and Y5) in the PVN and LH.
      1. Increases orexin A release and inhibits CRH
    2. Strong, but short lived effects
2. Paraventricular Nucleus (PVN)
  1. Appetite suppression
  2. α-MSH
    1. Released from the arcuate nucleus and suppresses appetite by inhibiting orexin A (which increases feeding) release from the LH, and increasing CRH (which decreases feeding) from the PVN
    2. Binds to melanocortin receptors (MC4) in the PVN and LH
      1. Receptors important as mutations in these, as well as receptor antagonists may cause hyperphagia and obesity
        MC4 agonists are potential therapeutic agents for obesity
3. Arcuate nucleus regulates indirectly, via the PVN and LH. Its neuropeptides are released into the nuclei, affecting the release of other neuropeptides. Opposite effects on the PVN and LH
4. When bound to its receptor in the arcuate nucleus, leptin has the opposite effects on appetite suppressing and enhancing neuropeptides. It therefore decreases feeding by directly and indirectly affecting the release of various neuropeptides in many hypothalamic nuclei
Two main views on how appetite is regulated
1. Depletion - Repletion Model
  1. Feeding due to decreased levels of energy sources (storage?)
2. Caloric Homeostasis Model
  1. Feeding due to decreased 'satiety signals' produced from the last meal. This would serve to maintain constant levels of free and stored energy sources

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Appetite Regulation

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	Erstellt von Lydia Buckmaster vor fast 11 Jahre