Exercise can reduce belly fat, but not when the drug blocks IL-6

Three months of endurance exercise on a stationary bicycle reduced abdominal visceral fat in obese patients, but not if they also received tocilizumab(RoActemra, Roche), an antibody that blocks interleukin-6 (IL-6) receptors, in a new research trial.

"To our knowledge, this is the first study to show that IL-6 plays a physiological role in regulating visceral fat mass in humans," lead author Anne-Sophie Wedell-Neergaard, MD, PhD, of the University of Copenhagen, Denmark, said in a statement from her institution released at the same time the study was publishedin the December27 Cellonjournal.

"We all know that exercise contributes to better health," she continued, "and now we also know that regular exercise reduces abdominal fat mass and thereby potentially reduces the risk of cardiometabolic disease.

According to Wedell-Niergaard, doctors should tell patients: "When you start exercising, your body weight may increase because of an increase in muscle mass. So, in addition to measuring total body weight, it would be helpful, if not more important, to measure waist circumference to monitor the loss of visceral fat mass and stay motivated."

This study also "raises the question of a potentially important side effect of IL-6 receptor antibodies such as tocilizumab" (i.e., they block the belly-shrinking effect of exercise in obese patients), the researchers note.

Tocilizumab also increased total cholesterol and LDL cholesterol levels compared with placebo in both the participants in the "with exercise" and "without exercise" groups.

However, it remains to be seen whether these effects are true for non-obese patients.

IL-6 and the effect of exercise on waistline weight loss

Abdominal obesity with visceral fat surrounding internal organs, Wedell-Niergaard and colleagues write, is associated with an increased risk of cardiometabolic disease, cancer, dementia, and earlier death.

On the other hand, physical exercise stimulates lipolysis, which is often associated with the action of epinephrine.

Researchers suggested that IL-6, which is released by skeletal muscles during exercise, may play a role in exercise-induced decreases in visceral abdominal tissue mass.

To test this, they assigned 67 physically inactive adults at their center who had a waist circumference of ≥88 cm for women or ≥102 cm for men to one of four groups:

• No exercise plus placebo (18 patients)

• No exercise plus tocilizumab (18 patients)

• Exercise plus placebo (16 patients)

• Exercise plus tocilizumab (15 patients)

Exercise consisted of several 45-minute endurance workouts on a supervised exercise bike per week for 12 weeks.

Tocilizumab (8 mg/kg body weight, diluted in saline) and saline placebo were administered as three monthly injections administered over 1 hour.

Five patients in each exercise refusal group and two patients in each exercise group dropped out or did not adhere to the study protocol, resulting in 53 patients selected for data analysis.

The mean age of the patients was 44 years and the mean body mass index was 33 kg/m. Three quarters (40/53) of the participants were women.

Researchers measured visceral fat mass using MRI at the beginning and end of the study.

After 12 weeks, visceral fat mass had decreased by 225 g, or 8%, in the group with exercise and placebo compared to the group without exercise and placebo.

The 8% reduction in visceral adipose tissue with exercise was lower than the 15% to 20% reduction reported in other studies, probably because of longer exercise sessions in other studies, the researchers suggest.

However, when patients received the IL-6 blocker tocilizumab, no decrease in exercise-induced visceral tissue mass was observed. In contrast, visceral adipose tissue increased by 278 g in the exercise plus tocilizumab group than in the exercise plus placebo group.

However, IL-6 blockade had no effect on the improvement of cardiorespiratory fitness indices, which were similar in both exercise groups.

The authors caution that this study is exploratory in nature and includes a small number of participants. Nevertheless, the results were similar for both sexes.

In addition, chronic elevation of IL-6 at low levels is seen in patients with severe obesity, type 2 diabetes and cardiovascular disease, the researchers note, so "it is likely that IL-6 may act differently in healthy and sick people."

Nevertheless, "this study solidified the physiological role of IL-6 as a lipolytic factor in people with abdominal obesity and highlights a potentially important metabolic consequence of IL-6 blockade."

"It remains to be seen," they conclude, "whether IL-6 regulates visceral adipose tissue mass in people with any waist circumference.

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