6.6.2 Hormones Continued

• Leptin is a hormone that is secreted by fat storage cells known as adipose cells
• The concentration of leptin in the blood is controlled by the amount of adipose tissue in the body
• As we eat food over a period of time, adipose cells store fats in the form of lipids
  • As adipose cells fill up, they secrete more leptin
  • This leptin circulates in the blood and targets groups of cells in the hypothalamus that are responsible for controlling appetite
  • It does this by binding to receptors in the membranes of these cells
  • This inhibits appetite and causes the sensation of hunger to be suppressed, or stopped

• If food intake is low over a period of time, the lipid reserves in adipose cells are used up and the adipose cells become empty again
  • As adipose cells empty and shrink, they secrete less leptin
  • The suppression of appetite stops, and the sensation of hunger returns

• As leptin inhibits appetite and causes the sensation of hunger to be suppressed, it was once thought that clinical obesity could be controlled by injecting patients with leptin
• Early trials in mice showed promise
  • Mice with a genetic leptin deficiency were shown to be less active and to gain weight faster than mice without this deficiency
  • Individuals with leptin deficiency lost 30% of their body mass when injected with leptin

• However, clinical trials to test whether this could be an effective treatment for obesity in humans found it to be ineffective

Reasons for the failure to control obesity with leptin injections

• Unlike in mice, most obese humans have very high concentrations of leptin in their blood
  • There are some human individuals who have problems with leptin production, but these are the exception rather than the rule

• It seems as though their bodies have become resistant to the effects of the hormone
  • The target cells in the hypothalamus become resistant to leptin and therefore fail to respond to it
  • This leads to a lack of appetite suppression, causing a continuous sensation of hunger and excessive food intake

• This means that injections of extra leptin fail to control obesity in the majority of obese patients
• Other problems with the clinical trials included
  • The need to inject leptin several times a day
  • Irritation at the injection site
  • Regain of any weight lost after the end of the trial

• It is always important to remember that while other mammalian research models such as mice are important, they are not always perfect  

• Many physiological processes and behavioural patterns occur in regular, daily rhythms in organisms throughout the plant and animal kingdoms
  • Many animal species are only active for a specific part of the 24-hour cycle e.g. nocturnal animals are only active at night

• Humans are adapted to live in a 24-hour cycle and many aspects of our physiology and behaviour, including physical activity, sleep, body temperature, and secretion of hormones, follow specific and regular cycles throughout the 24-hour period
  • These daily cycles are known as circadian rhythms

• In humans, many circadian rhythms are influenced by the hormone melatonin
  • Melatonin is secreted by the pineal gland, which is located in the brain
  • Melatonin secretion increases in the evening in response to darkness and decreases at dawn in response to light

• Although melatonin affects many aspects of human physiology and behaviour, one of the main circadian rhythms it controls is our sleep-wake cycle
  • Increasing melatonin levels lead to feelings of tiredness and promote sleep
  • Decreasing melatonin levels lead to the body's preparation for waking up and staying awake during the day

• Experiments have also suggested that
  • Increased melatonin at night contributes to the night-time drop in core body temperature in humans
  • Melatonin receptors in the kidney enable melatonin produced at night to cause the night-time decrease in urine production in humans
  • Melatonin is still released in the absence of light and dark signals, but on a slightly longer cycle than the usual 24 hours
    • Subjects living in the dark with no access to natural daylight still release melatonin on a roughly 24 hour cycle
    • This suggests that the role of light is to reset the melatonin system every day to keep the circadian rhythm in line with daylight hours

• Jet lag is the term used to describe the various symptoms a person can experience after crossing multiple time zones during a long flight
• The symptoms can include:
  • Difficulty in remaining awake during the day
  • Difficulty in sleeping during the night
  • General fatigue
  • Irritability
  • Headaches
  • Indigestion

• Jet lag occurs because the body's circadian rhythms are still set to the timing of day and night in the time zone from which the person has just departed, rather than the time zone they have just arrived in
• Jet lag usually only last for a few days as the body adjusts to the new day and night regime
• Melatonin tablets are sometimes taken to prevent or reduce jet-lag symptoms
  • The tablets are normally taken just before going to sleep
  • Some clinical trials have shown this use of melatonin to be effective in promoting sleep and reducing other jet lag symptoms
  • However, the safe and appropriate use of this medication still needs more testing