Andreas Birkenfeld looking at a mouse sitting on a stool in his laboratory at the University Hospital Dresden

Bodyweight The INDY gene

A nice trim figure despite consuming lavish amounts of our favourite fatty foods – will we soon be able to forget dieting and be like the mice in Andreas Birkenfeld's laboratory? the INDY gene, which is an acronym for ‘I’m Not Dead Yet’, is responsible for a transporter which carries metabolic building blocks through the membrane of liver cells and some other cells. If we suppress it, the cell is deprived of fuel for energy production. By Katharina Kämpfer

Professor Birkenfeld, how are your mice?
Andreas Birkenfeld: They’re doing fine. Even though they get plenty of lard – which is considered to be ‘bad’ fat of the saturated variety – our mice are lean and fit. They move around a lot and have a powerful appetite. At an advanced age, they look significantly younger and stay healthier than mice on a normal diet.

How do they manage to stay so trim?
Our research group at the University Hospital in Dresden has switched off a gene in these mice that is important for the energy consumption of the cell – the INDY gene, which is an acronym for ‘I’m Not Dead Yet’. It is responsible for a transporter which carries metabolic building blocks through the membrane of liver cells and some other cells. If we suppress it, the cell is deprived of fuel for energy production. The cell absorbs less energy, the body puts on less weight and does not develop insulin resistance or atherosclerosis. In the first batch of mice, we switched off the gene by making changes to the genome. Now we are beginning to suppress it by means of a drug. If all goes well, we could be testing this blocker on humans in three to five years’ time.

Do you think we may be able to eat as much as we like in future then?
The drug will certainly only be prescribed to very specific groups of patients, for example those with a fatty liver, which is caused by extreme obesity. An estimated one-third of Americans have a fatty liver. This can progress to fibrosis, then cirrhosis and ultimately to a liver carcinoma. In the initial stage, it can be treated by weight reduction, but our experience shows that most patients do not manage to lose weight over the long term. You can’t simply advise a patient weighing between 150 and 200 kilos to just take up jogging. In such patients, the drug could be used to prevent fatty liver, diabetes and cardiovascular problems, and to help them resume a normal life.

So the rest of us have to carry on watching our diet?
Well, everyone else needs to continue paying attention to their calorie intake. You could say that we are victims of evolution. For millennia, it was advantageous to store a lot of energy. It will certainly take another thousand years before our bodies adapt to this new lifestyle. Until then, we have to be careful about how much we eat. Anyone who wants to stay healthy into old age, to stave off cancer and brain cell degeneration, should reduce their calorie intake by as much as 20 percent. There is no quick and easy fix. Recent studies have shown that fasting for five days in the month has the same beneficial effect. That means reducing intake to 1,000 calories which should be as healthy as possible and contain all the vitamins and trace elements. You can then binge for the rest of the month

Andreas Birkenfeld, Professor of Metabolic and Vascular Medicine at the University Hospital Dresden and Director of the GWT-TUD Centre for Clinical Trials

Andreas L. Birkenfeld

wants to build a bridge between laboratory and hospital bed. The Professor of Metabolic and Vascular Medicine at the University Hospital Dresden and Director of the GWT-TUD Centre for Clinical Trials was awarded the Ferdinand Bertram Prize by the German Diabetes Society in 2015.
uniklinikum-dresden.de