Brent Cornell

    
Leptin is a hormone produced by adipose cells that regulates fat stores within the body by suppressing appetite

• Leptin binds to receptors located within the hypothalamus to inhibit appetite and thereby reduce food intake

Overeating causes more adipose cells to formed and hence more leptin is produced, suppressing further appetite

• Conversely, periods of starvation lead to a reduction in adipose tissue and hence less leptin is released, triggering hunger

As obese people are constantly producing higher levels of leptin, their body becomes progressively desensitised to the hormone

• This means they are more likely to feel hungry, less likely to recognise when they are full and are hence more likely to overeat
• Leptin resistance also develops with age, increasing the potential for weight gain later in life (e.g. the ‘middle-age spread’)

The Role of Leptin in Hunger and Satiety

    
Because leptin suppresses appetite, it was considered as a form of treatment for individuals with clinical obesity

• Theoretically, leptin injections would reduce hunger and limit food intake in obese individuals, leading to weight loss

Mice Experiments

Leptin trials were initially conducted by surgically fusing the blood circulation of obese and healthy mice (parabiosis)

• This experiment was conducted using mice that were either obese due to a leptin gene mutation or a defective leptin receptor

When the obese mouse with no leptin was parabiotically fused to a healthy mouse:

• Leptin in the blood of the healthy mouse was transferred to the obese mouse
• The obese mouse responded to the leptin and began to lose weight, demonstrating the potential viability of leptin treatment

However, when the obese mouse with a defective leptin receptor was parabiotically fused to a healthy mouse:

• Leptin was transferred to the healthy mouse (the obese mouse overproduced leptin to compensate for low receptor sensitivity) 
• The obese mouse remained obese as its body could not respond to leptin
• The healthy mouse became emaciated due to the abnormally high levels of leptin transferred into its bloodstream

Human Experiments

Most humans have naturally high levels of leptin in the bloodstream

• When linked to leptin activity, most cases of obesity are caused by an unresponsiveness to leptin and not a leptin deficiency 
• Hence, in clinical trials, very few participants experienced significant weight loss in response to leptin injections
• However, many patients did experience adverse side effects from leptin injections, including skin irritations
• For these reasons, leptin treatments are not considered to be an effective way of controlling obesity