The research team led by Annette Schürmann, Robert Schwenk and Christian Baumeier of the DIfE recently published its findings in the journal Biochimica et Biophysica Acta (Baumeier et al. 2015, http://dx.doi.org/10.1016/j.bbalip.2015.01.013). The study was funded by the German Center for Diabetes Research and the German Research Foundation.
In many people, obesity leads to insulin resistance, the precursor of type 2 diabetes. As has long been known, caloric restriction along with intermittent fasting can reverse an already existing insulin resistance. However, it has not been adequately studied just why insulin sensitivity is improved through intermittent fasting.
To investigate more precisely the molecular mechanisms that underlie the positive effect of intermittent fasting, Schürmann’s team conducted a study on obese mice with a genetic predisposition to obesity and type 2 diabetes.
When the overweight, already insulin-resistant mice were allowed unlimited access to high-fat food only every second day, and on the other days were only allowed to drink water, they became more sensitive to insulin and were protected against type 2 diabetes.
“However, their siblings that were allowed to eat ad libitum became insulin resistant, and almost half developed type 2 diabetes within a short time,” said Annette Schürmann, who heads the Department of Experimental Diabetology at the DIfE.
As the researchers observed, fasting has an especially positive effect on liver lipids, by significantly reducing the amount of these lipids which are suspected to promote insulin resistance. In the liver, lipids are found in the form of tiny droplets, which are in turn associated with different protein molecules. As the researchers noted, not only the size of the lipid droplets but also the composition of the protein molecules associated with the droplets changed. “We assume that this altered protein composition is responsible for the beneficial effect,” said diabetes researcher Annette Schürmann. However, further studies are necessary to further elucidate this molecular relationship.
“In addition, our data indicate that fasting clearly improves the energy metabolism. The muscles of the mice were able to switch much faster between the burning of carbohydrates and fats. This greater metabolic flexibility helps in healthy people to keep harmful free lipid levels low. This in turn can prevent insulin resistance,” added co-author Robert Schwenk.

* Insulin resistance is defined as the diminished ability of muscle, liver and lipid cells to respond to the hormone insulin.
Insulin regulates the absorption of sugar (glucose) from the blood into the tissues and also plays an important role in lipid metabolism. If the cells no longer react sufficiently to insulin and the body is no longer able to compensate for this through enhanced insulin production, the metabolism gets out of control, a condition referred to as type 2 diabetes.