Molecule interleukin-6 in the body makes losing weight easier with regular exercise

LONDON: Some of you may have made a New Year's resolution to hit the gym to shed that unwanted belly fat, and now researchers have revealed how exercise produces this desired effect.

A signalling molecule called interleukin-6 plays a critical role in this process, according to the study published in the journal Cell Metabolism.

A 12-week intervention consisting of bicycle exercise decreased visceral abdominal fat in obese adults, said researchers from the University of Copenhagen in Denmark.


This effect was abolished in participants who were also treated with tocilizumab, a drug that blocks interleukin-6 signalling and is currently approved for the treatment of rheumatoid arthritis.

Moreover, tocilizumab treatment increased cholesterol levels regardless of physical activity.

"The take home for the general audience is 'do exercise,'" said Anne-Sophie Wedell-Neergaard of the University of Copenhagen.

"We all know that exercise promotes better health, and now we also know that regular exercise training reduces abdominal fat mass and thereby potentially also the risk of developing cardio-metabolic diseases," said Wedell-Neergaard.

Abdominal fat is associated with an increased risk of not only cardio-metabolic disease, but also cancer, dementia, and all-cause mortality, researchers said.

Physical activity reduces visceral fat tissue, which surrounds internal organs in the abdominal cavity, but the underlying mechanisms have not been clear, they said.

Some researchers have proposed that a "fight-or-flight" hormone called epinephrine mediates this effect.

However, researchers suspected that interleukin-6 could also play an important role because it regulates energy metabolism, stimulates the breakdown of fats in healthy people, and is released from skeletal muscle during exercise.

The researchers carried out a 12-week, single-centre trial in which they randomly assigned abdominally obese adults to four groups.

A total of 53 participants received intravenous infusions of either tocilizumab or saline as a placebo every four weeks, combined with no exercise or a bicycle routine consisting of several 45-minute sessions each week.


The researchers used magnetic resonance imaging to assess visceral fat tissue mass at the beginning and end of the study.

In the placebo groups, exercise reduced visceral fat tissue mass by an average of 225 grammes, or 8 per cent, compared with no exercise.

However, tocilizumab treatment eliminated this effect.

In the exercise groups, tocilizumab also increased visceral fat tissue mass by about 278 grammes compared with placebo.

In addition, tocilizumab increased total cholesterol and "bad" low-density-lipoprotein (LDL) cholesterol compared with placebo, in both the exercise and no-exercise groups.


"To our knowledge, this is the first study to show that interleukin-6 has a physiological role in regulating visceral fat mass in humans," Wedell-Neergaard said.

Interleukin-6 can have seemingly opposite effects on inflammation, depending on the context.

For example, chronic low-grade elevations of interleukin-6 are seen in patients with severe obesity, type 2 diabetes, and cardiovascular disease.

"The signalling pathways in immune cells versus muscle cells differ substantially, resulting in pro-inflammatory and anti-inflammatory actions, so interleukin-6 may act differently in healthy and diseased people," Wedell-Neergaard said.