17 October 2006

Clues to appetite control

Struggling to control how much you eat? New research is slowly, but systematically, uncovering the extremely complex factors that control human appetite. DietDoc investigates.

While doing research on food cravings, I came across a number of fascinating scientific articles describing appetite control.

New research is slowly, but systematically, uncovering the extremely complex factors that control human appetite.

Why this research is important
Obesity is one of the most serious problems facing the western world. Overweight or obesity can increase the risk of type 2 diabetes, hypertension, stroke, heart and respiratory problems, gall bladder disease, osteoarthritis, sleep apnoea, and certain types of cancer.

Research into what controls human appetite and the urge to eat or overeat is, therefore, of vital importance to halt the obesity epidemic.

If researchers can identify what causes us to overeat and can design medications to counteract the factors that prompt overeating, we would have a solution to this escalating problem.

Appetite-controlling factors
The research into appetite control has uncovered a wide range of chemical factors that play a role in overeating.

Most of these factors, or so-called neurotransmitters, are hormones, hormone-like substances or neuropeptides. A neuropeptide, as the name implies, is made up of peptides (amino acids that are strung together, which have an effect on the central nervous system, i.e. "chemical messengers").

A very complex system
It is rapidly becoming evident that appetite control is a very complex system. In a review, Wilding (2002) lists nine neurotransmitters that increase food intake and nine neurotransmitters that decrease food intake, which have been identified to date.

Therefore, at present, we know of 18 factors that may influence how much, or how little, we eat. This is a formidable array of chemicals that all act on one human function, namely appetite control.

Why humans are programmed not to lose weight
One discovery that bodes ill for quick weight-loss solutions is that humans have been programmed for thousands of years to conserve energy and prevent weight loss.

According to Wilding, human beings have "a biased homeostatic system". Scientists are finding more and more evidence that our bodies are programmed to "conserve energy, seek food in times of need, and store energy in times of plenty".

While we are excellent hoarders of energy in the form of body fat, nothing in the evolution of homo sapiens has encouraged us to develop systems to promote weight loss. In fact, as a species, we have very few regulatory systems that decrease food intake in the long term.

Neurotransmitters that promote food intake
There are a host of neurotransmitters that promote food intake. For example, the hormones insulin and leptin will promote overeating via a part of the brain called the hypothalamus.

a) Leptin
Leptin is a hormone that is produced by fat tissue in the body. When animals and humans lose weight, their leptin levels fall and this coordinates a response to seek out food and conserve energy. A lack of leptin, or of the receptor that reacts to its signals, is associated with severe obesity in experimental animals.

It would, therefore, seem logical to treat obese humans with synthetic leptin preparations. This has been tried in some studies. Unfortunately obese humans do not respond to leptin supplementation and in fact have high leptin levels, which has lead researchers to suggest that human obesity is most probably caused by leptin resistance.

In other words, overweight humans don't lack leptin, but the receptors that are supposed to react to its signal to stop eating, are resistant to transmitting this message.

b) Insulin
Insulin is another hormone that may promote weight gain, as is postulated when describing the metabolic syndrome.

This syndrome is characterised by weight gain, inability to lose weight, insulin resistance, and other metabolic derangements.

The gut hormones
Initially researchers believed that the gut (intestines) was inactive and not capable of producing complex appetite signal transmitters such as hormones and neuropeptides. However, ongoing research has overturned this approach.

Experts now know that the gut is capable of synthesising a whole array of neurotransmitters that all play a role in controlling appetite and food intake.

i) Grehlin
One example is grehlin – a hormone produced by the stomach that stimulates food intake and can cause obesity.

This is one of the reasons why people who have had stomach bypass procedures lose so much weight. On the one hand, their digestion of food is reduced; on the other hand, they are no longer able to produce grehlin.

ii) Pancreatic polypeptide and peptide YY
Then there are the anorectic compounds called pancreatic polypeptide and peptide YY, which have been used in experiments to reduce food intake – both in obese and normal-weight control subjects.

Could these peptides be the answer to obesity? We don't know yet, but these anorectic peptides are being studied as potential anti-obesity solutions.

Opioid peptides and cannabinoids
Another class of peptides, called the opioid peptides, may also increase food intake, particularly of sweet-tasting foods. Then there are the cannabinoids which also increase food intake and are believed to be related to food addiction.

Research into pharmaceutical compounds that can counteract these cannabinoids is presently underway and may produce a solution to certain types of overeating.

Take-home message
The bottom line when it comes to appetite regulation and overeating and obesity, is that we now know that this is an extremely complex system in humans that may take a long time to unravel.

However, researchers are working round the clock to sort out which factors in the complex web of hormones and neurotransmitters can be used, or blocked by pharmaceutical products, to produce weight loss.

The good news is that there is tremendous pressure on researchers to find a solution to the obesity epidemic. There are already signs that some approaches may help overweight individuals curb their appetites and lose weight.

How soon we will have drugs that can switch off appetite-stimulating neurotransmitters and/or switch on appetite-depressing neurotransmitters, is not clear. However, scientists are on the right track and should come up with solutions sooner, rather than later. – (Dr Ingrid van Heerden, DietDoc, October 2006)

Wilding, J.P.H. (2002) Neuropeptides & appetite control. Diabetic Medicine, Vol 19, 619-627.

Read more:
Chemicals that control appetite
Obesity: not a simple issue


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