Obesity 161responsible for obesity. Some work using small animals has identified a
single gene which is associated with profound obesity (Zhang et al., 1994).
Other animal work has explored the impact of minor and major genes on
food intake and energy expenditure. However, for humans the work is still
unclear but tends to fall within three areas of research: leptin production,
genetic disorders, and candidate genes.
Leptin
One area of research has focused on the production of a protein called leptin,
which is thought to inhibit eating and regulate energy expenditure. Research
has shown that leptin levels are positively correlated with BMI and percen-
tage body fat, and are high in the obese and lowered in sufferers of anorexia.
Further, leptin levels fall in the obese when weight is lost (Considine et al.,
1995; Ferron et al., 1997). It has therefore been argued that obesity may result
from leptin resistance, with the high levels of leptin in the obese being ignored
by the body’s satiety mechanisms. In contrast, leptin deficiency has also been
linked to obesity. Two children have been identified with a defect in the
“ob gene” which produces leptin and is responsible for telling the brain to
stop eating (Montague et al., 1997). To support this, researchers have given
these two children daily injections of leptin, which has resulted in a decrease
in food intake and weight loss at a rate of 1–2 kg per month (Farooqi et al.,
1999). Similarly, Licinio et al. (2007) gave leptin replacement to three adults
with leptin deficiency and reported an initial reduction in food intake and
highly specific changes in the intake of macro- and micronutrients. Therefore,
both too much and too little leptin may result in weight gain and obesity.
Genetic disorders
An alternative train of research has focused on genetic diseases which have
obesity as part of their expression. Such diseases include Prader Willi
syndrome and Bardet-Biedel syndrome, and research has studied these
diseases as a means to map the genes involved in body weight. To date this
research is in its infancy.
Candidate genes
A final area of research has explored candidate genes which are a part of
the DNA molecule responsible for the production of polypeptide chains
central to a particular disease. To date some candidate genes have been
identified as linked to obesity, and research in this area will expand given
the development of marker libraries following the human genome project.