Abdominal (belly) fat is harmful to metabolic health. Exercise training reduces abdominal fat mass, but the underlying mechanisms have not been clear. According to a new study, published in the journal Cell Metabolism, a signaling molecule called interleukin-6 plays a key role in this process.
Wedell-Neergaard et al show that in abdominally obese people, exercise-mediated loss of visceral adipose tissue mass requires interleukin-6 (IL-6) receptor signaling. Given that abdominal fat is metabolically harmful to health, the study raises a potentially important side effect of IL-6 receptor antibodies, such as tocilizumab. Image credit: Wedell-Neergaar et al.
“We hypothesized that exercise-induced reductions in abdominal fat mass are mediated by interleukin-6, because it regulates energy metabolism, stimulates the breakdown of fats in healthy people, and is released from skeletal muscle during exercise,” said University of Copenhagen’s Dr. Helga Ellingsgaard and co-authors.
To test this idea, the researchers carried out a 12-week, single-center trial in which they randomly assigned abdominally obese adults to four groups.
A total of 53 participants received intravenous infusions of either tocilizumab (a drug that blocks interleukin-6 signaling and is currently approved for the treatment of rheumatoid arthritis) 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 scientists used magnetic resonance imaging to assess abdominal fat mass at the beginning and end of the study.
In the placebo groups, exercise reduced visceral fat tissue mass by an average of 225 grams, or 8%, compared with no exercise. But tocilizumab treatment eliminated this effect.
In the exercise groups, tocilizumab also increased visceral fat tissue mass by approximately 278 grams 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 abdominal fat mass in humans,” said study first author Dr. Anne-Sophie Wedell-Neergaard, also from the University of Copenhagen.
_____
Anne-Sophie Wedell-Neergaar et al. Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial. Cell Metabolism, published online December 27, 2018; doi: 10.1016/j.cmet.2018.12.007
