L7 - Leptin

  • Created by: BKW
  • Created on: 09-01-20 16:40
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  • l7 - Leptin
    • What is Leptin?
      • A tonic factor in the LT, energy is stored around internal organs under skin in adipose tissue (containing fat cells)
        • 1994 Leptin was identified as a factor released by fat tissue
      • it is a natural adiposity (body fat) signal
      • the means by which energy stores signal to the CNS to alter subsequent eating behaviour
    • What does it do?
      • reduces food intake
      • Endogenous leptin is released from fat cells when energy stores ^^^
      • Stimulates CNS receptors causing vvv in energy intake and ^^^ in energy expenditure
      • Leptin acts in a negative feedback loop for adipose tissue to counteract any increase in body fat
    • ob/ob Mice
      • Leptin is encoded by the ob/ob gene
      • The mice have ob gene = ob/ob syndrome
        • Characterised by hyperphagia, vvv energy expenditure leading to obesity
        • 2 distinct features  = sensitivity to effect of exogenous leptin responding with vvv in food intake & vvv obesity
      • They have functioning leptin receptors they just don't respond to it
    • Human obesity&leptin
      • Is human obesity due to leptin deficiency or defect in leptin signalling?
        • only a small no of obese humans with leptin deficiency due to ob/ob gene mutation have been identified
          • Montague et al - identified 2 severely obese Pakistani cousins whose plasma leptin levels were very low compared to normal lean children due to a truncation mutation in gene
          • Strobel et al identified a missense mutation in the leptin gene of 3 morbidly obese members of an extended Turkish family
          • Farooqi et al - daily administration of recombinant human leptin to achieve 10% of predicted normal leptin concentrations - treatment was well tolderated, sustained vvv in appetite, food intake and body weight. vvv in body weight was almost  entirely due to fat loss & no effect on energy expenditure
      • OB-R mutations
        • Mutations effecting leptin receptor gene also rare
          • Clement et al - identifies mutation in leptin receptor gene results in a truncated receptor lacking both transmembrane & intercellular domains
            • patients with this have early onset morbid obesity and no pubertal development
              • these people do not benefit from leptin treatment
      • leptin resistance NOT leptin deficiency?
        • Evidence rodents can develop leptin resistanvce under certain conditions eg saturation of brain leptin transporters with voluntary  obesity
    • does it enhance satiety?
      • Leptin vvv food intake but the mechanism is largely unknown
      • kahler et al demonstrated chronic admin of leptin in 24 male rats vvv food intake by selectively vvv meal size. nocturnal spontaneous meaal size vvv by 21-34% but no effect of frequency or duration
        • indicates recombinant leptin affects mechanism controlling meal size in male rats = satiety


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