Intermittent fasting, without restricting overall calorie intake, has been found to reduce weight and improve metabolism. A new investigation hunts down the molecular mechanisms behind these physiological benefits.

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Fasting intermittently has several health benefits, but why?

Our modern lifestyle, combined with longer waking hours, means that the enforced period of fasting while we sleep has steadily been reduced. This, along with the poor-quality Western diet and more time spent sedentary, has dramatically increased the prevalence of obesity and metabolic disease.

Over recent years, fasting has been shown to impart a number of health benefits.

Many clinicians hope that by modifying aspects of fasting — such as how long to fast for, what to eat between fasts, and when to fast — it may be possible to design methods of combating obesity and metabolic disorders.

Intermittent fasting is believed to share many of its health benefits with prolonged fasting. It has, for instance, been shown to reduce oxidative stress and inflammation.

Other studies have demonstrated that intermittent fasting increases insulin sensitivity and protects nerve cells from certain types of damage. It may also slow aging and reduce the risk of age-related diseases.

Intermittent fasting without a reduction in calorie intake can be a preventative and therapeutic approach against obesity and metabolic disorders.”

Study co-author Kyoung-Han Kim

Because of these, and other, recent findings, the so-called 5:2 diet — which involves 5 days of normal eating followed by 2 days of fasting — has become popular.

Evidence in favor of intermittently restricting calorie intake is growing, but the mechanisms through which it imparts its benefits are still unclear. Recently, a research team led by Hoon-Ki Sung — of the Department of Laboratory Medicine and Pathobiology at the University of Toronto in Ontario, Canada — set out to look under the hood of intermittent fasting.

Investigating the molecular changes that might underpin intermittent fasting’s effects, their results are published this week in the journal Cell Research. Of particular interest were the roles of brown and white fat.

White fat is essential for storing excess energy and releasing lipids when the need arises. However, it is also associated with obesity and type 2 diabetes. Brown fat, on the other hand, burns energy and has been suggested as a potential candidate for the treatment of obesity and metabolic diseases.

Recent studies have shown that, under certain circumstances, white fat can be converted into brown (and sometimes beige) fat. This process — referred to as browning — is coming under scrutiny as a potential avenue to reduce obesity.

For the current experiment, the team put mice into two groups: an intermittent fasting group and a control group. The former group was given no food for 1 day and was then fed for the next 2 days. The latter group was fed daily. The study continued for 16 weeks.

Across the 4-month period, both groups of mice consumed the same number of calories; those in the intermittent fasting group were able to catch up during their 2 days of eating. By the end of the study, the mice in the intermittent fasting group weighed significantly less than the control mice.

The researchers also found that, in the intermittent fasting group, glucose metabolism was more stable and insulin sensitivity was increased, when compared with controls.

There were other significant differences, too, such as the fact that intermittent fasting mice had healthier livers with less lipid buildup.

Importantly, mice in the intermittent fasting group had a lower percentage of white fat, because it was being converted into brown fat.

Perhaps surprisingly, when the team ran a similar experiment using obese mice, they found the same types of benefits after just 6 weeks of intermittent fasting.

Next, the team wanted to understand the physiological and metabolic changes that underpinned the benefits found in the intermittent fasting group — particularly the browning of white fat cells.

Alterations in immune-related gene pathways within fat cells appeared to be at the root of the changes.

In particular, during fasting periods, there was an increase in vascular growth factor, which helps to form blood vessels and trigger anti-inflammatory macrophages. Anti-inflammatory macrophages encourage fat cells to burn fat stores and create heat — and, as the name suggests, reduce inflammation.

Strikingly, these fasting-stimulated changes in the growth of vascular cells and subsequent immune alterations occur even after a single cycle of 24-hour fasting, and are completely reversed when mice start eating again.”

Study co-author Yun Hye Kim

The researchers are keen for research into intermittent fasting to continue; there are a number of questions they would like answered.

For example, it is difficult to extrapolate the ideal length of fasting from mice to humans, so more clinical work will need to be done. Also, how long the beneficial effects remain once the diet ends needs to be ascertained.

In the future, research into the mechanisms at work underneath intermittent fasting could help to tailor programs to treat obesity and metabolic conditions such as type 2 diabetes. Because of the prevalence of these conditions in the United States, results are eagerly awaited.