• 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