Every third person on earth is too fat. In the last 30 years the number of overweight people has increased worldwide. While in 1980 28.8 percent of men and 29.8 percent of women carried too many kilos around with them, already by 2013 36.9 percent of men and 38.0 percent of women showed a BMI of over 25 kg/m2. Children and young people are also continuously getting fatter. This trend can be observed not only in the industrialised countries, but also increasingly in developing countries, as a study recently published in The Lancet showed. The sobering realisation: In the last 33 years not one single nation has been able to reduce the number of its overweight inhabitants. Time to break new ground?
Calorie balance is not everything
Of course, calorie balance in the emergence of obesity does play a central role, but the problem cannot be exclusively reduced to being a dietary one. Because unlike perhaps commonly believed, it’s not Americans or Mexicans who are the fattest folk on earth. Rather, the small island nations of Tonga, Samoa and Kiribati top the list of countries with the most overweight population. Apart from cultural peculiarities such as having different ideals of beauty to those in Western countries, the girth of the islanders could also have genetic causes, because until the British arrived in the 19th century the island nations existed for a long time practically alone – in genetic terms as well.
When the islets were overtaken about 4000 years ago by the first settlers, probably only those survived who could most effectively convert their food into energy. This genetic survival advantage was passed on within the groups of island people from generation to generation – right until today. When this genetically standardised configuration meets a Western-type diet, it has fatal consequences for the body form of the islanders.
Pill against obesity
The education of the public about a healthy lifestyle is an important element in the fight against the massive increase of obesity. In addition, scientists have been trying for quite some time to get control of the serious problem from another angle – with a pill against obesity. The protein FFA4 could be one of the actors which are instrumental in the expression of obesity, because it is has the capability to stimulate various physiological activities: FFA4 can both stimulate the production of appetite-controlling hormones, as well as hormones which control the absorption of nutrients from the gut. The protein occurs in the membrane of intestinal, immune and fat cells and is activated by long-chain free fatty acids which we ingest through food. Where present, FFA4 ensures that hormones are released which slow the appetite and increase the absorption of sugar from the blood.
Pre-selection of potential agents using computer
“In some people, this protein does not function properly. They have a greatly increased risk of becoming obese and of getting diabetes type 2”, says Bharat Shimpukade from the University of Southern Denmark. Together with scientists from the University of Glasgow, Shimpukade searched for molecules that can activate FFA4. Yet this is really not such an easy task. “There are an almost infinite number of molecules which we synthesise and would then need to be checked for their ability to activate FFA4”, says Shimpukade. In order to circumvent this tedious laboratory work, scientists have developed a different strategy: “We have developed a computer model of FFA4, with which we can test on the screen whether a molecule can bind to FFA4. In this way we can test thousands of molecules within a very short time before we examine their function in the laboratory. This will significantly accelerate the development of a drug against obesity and type 2 diabetes”, predicts Bharat Shimpukade.
Perfect activator soon found
Already in 2012 the scientist and his colleagues revealed to the public the first selective activator of FFA4, which is now being used to study the functions of the protein. The molecule can indeed properly activate FFA4, it is not suitable as a drug agent however because it is not sufficiently stable in the human body. “We need a compound with greater water solubility and improved stability”, says Shimpukade, adding: “It has to remain intact in the body until it has done its job. On the other hand, the compound should also not be stable forever”. With the help of the computer model he will soon find the optimal molecule, Bharat Shimpukade is sure. Will it be the solution to this massive global problem though?