FAT LOSS, BIOLOGICAL INFLUENCE: THE SATIETY GENE
All of the above suggests that obesity is a ‘polygenic’ disorder, or that there are a number of genetic components to obesity. Major excitement was aroused in scientific circles in late 1994 because of the identification of a gene apparently linked to ’switching’ on and off hunger, called a satiety gene. The history of this discovery is fascinating and helps provide an understanding of the complexity of the problem.
It has been known for some time that substances must exist in the blood which signal the state of energy stores to the brain so that hunger can be turned on and off. In the early 1950s, a mechanism called an ‘appestat’ was hypothesised to operate like a thermostat in ’switching off hunger after a certain level of food intake. This was further supported in the 1960s and 1970s by some ingenious research carried out by Dr Douglas Coleman at the Jackson Laboratory in Maine with two inbred strains of obese mice (called ‘db’ for diabetes and ‘ob’ for obese). Coleman joined these mice with normal lean mice (a process called ‘parabiosis’) so they both had the same circulatory system. In doing so, strange things happened.
When a normal mouse was joined with a ‘db’ strain mouse, the lean mouse actually starved to death—even in the presence of abundant food. This suggested that the ‘db’ strain had an over-supply of some substance in the blood to tell it to stop eating, but that this wasn’t working in the ‘db’ mouse. When an ‘ob’ and a ‘db’ mouse were joined, the ‘ob’ mouse died from starvation, but the ‘db’ mouse increased its weight by over-eating. Again, this suggests that the ‘db’ mouse was over-supplying a ’switch off substance which was not working with it, but which worked excessively well with the ‘ob’ mouse. Finally, when a normal mouse was joined with an ‘ob’ mouse, the ‘ob’ mouse lost weight and became normal. All this suggested that normal mice have a normal amount of a substance which the ‘ob’ mouse does not have, and which the ‘db’ mouse has too much of, but which has no effect (i.e. does not reach a receptor) in the ‘db’ mouse.
Dr Jeremy Friedman and his team from Rockefeller University in New York then isolated a gene which codes for the production of a protein from fat cells, which tells the brain when satiation has been reached. The protein has since been identified, synthesised and injected into obese mice and found to reduce their body weight The substance has been called ‘leptin’ (after the Greek word ‘leptos’ meaning ‘thin’), and the race is now on to develop drugs which may be useful in human obesity. Most scientists, however, warn that the discovery is not likely to be as simple a remedy as some have claimed, and that much more work still needs to be done.
There are likely to be few, if any, human equivalents of the ob or db mice which have major single gene abnormalities. In humans, there may however, be gene variations which result in some people being less able than others to switch off their appetite. Genetic influences in human obesity are indicated by some simple factors such as:
• Presence of lifetime or long term obesity in one or both parents. Studies have shown that the chances of being obese are around 80 per cent if both parents are obese, 40 per cent if one parent is obese and only 7 per cent if neither parent is obese.
• Presence of obesity since childhood. Genetically influenced obesity is usually manifest early in life, particularly before or around adolescence. For this reason someone who has always had a problem, particularly if the problem is also in the immediate family, is more likely to be genetically influenced.
• Presence of type I obesity. Abdominal obesity, particularly in men, is generally regarded as being environmentally determined. Ovoid-shaped fatness, together with the factors mentioned above, may suggest genotypical influences.
Although the factors mentioned above provide no certainty about genetic influence, they may give some indications that fat loss is likely to be a more difficult proposition in an individual who is genetically predisposed to fatness and that efforts to prevent fat gain may need to be lifelong; therefore, this person needs long term goals which are realistic. Special attention may also need to be given to hunger and behavioural cues and to maintenance of body weight after slimming.
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