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
- A tonic factor in the LT, energy is stored around internal organs under skin in adipose tissue (containing fat cells)
- 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
- only a small no of obese humans with leptin deficiency due to ob/ob gene mutation have been identified
- 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
- patients with this have early onset morbid obesity and no pubertal development
- Clement et al - identifies mutation in leptin receptor gene results in a truncated receptor lacking both transmembrane & intercellular domains
- Mutations effecting leptin receptor gene also rare
- leptin resistance NOT leptin deficiency?
- Evidence rodents can develop leptin resistanvce under certain conditions eg saturation of brain leptin transporters with voluntary obesity
- Is human obesity due to leptin deficiency or defect in leptin signalling?
- 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
- What is Leptin?
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