Editors' ChoiceMetabolism

IL-6: A hack to body fat and exercise?

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Science Translational Medicine  23 Jan 2019:
Vol. 11, Issue 476, eaaw5316
DOI: 10.1126/scitranslmed.aaw5316


The IL-6 receptor antibody tocilizumab abolished the ability of exercise to reduce visceral fat and cholesterol levels in obese individuals.

Living a sedentary lifestyle is the biggest risk factor for obesity, a condition which predisposes to cardiovascular and other metabolic diseases. Although physical exercise is the most common intervention to tackle obesity, the mechanisms that explain these benefits of exercise are elusive. A randomized clinical trial reported by Wedell-Neergaard et al. demonstrated that the immune system cytokine interleukin 6 (IL-6) may explain the link between exercise and fat metabolism.

In this trial, abdominally obese participants were randomly allocated into four groups: those who participated in periodic ergometer bike training exercise versus no exercise, while also subjected to regular injections of an IL-6 receptor antibody tocilizumab (to block IL-6 signaling) or a placebo over the course of 12 weeks. The investigators observed that tocilizumab abolished the beneficial effects of endurance exercise in reducing visceral fat mass (fat tissue in the abdomen and surrounding internal organs) to levels seen in participants who did not participate in exercise. Similar trends were also observed in total body weight and fat mass measured in other body areas, and lean body mass was unaffected.

Investigators next examined the metabolic profiles in these four groups of participants. Participants on exercise and tocilizumab saw a complete reversal of blood cholesterol to concentrations comparable to physically inactive groups, while other metabolic profiles such as triglycerides, fasting blood glucose, and insulin levels were unchanged. To demonstrate a direct effect of IL-6 signaling blockade in counteracting the effects of exercise on fat mass, the authors showed that tocilizumab did not affect cardiorespiratory fitness in either the physically inactive or exercise groups.

This study suggests that the IL-6 is a key regulator between exercise and fat metabolism. Future studies of IL-6 in exercise should take into consideration the influences of other metabolic diseases, genetic predisposition, and age or sex differences that could affect fat metabolism. These findings could further our understanding of the potential adverse effects of patients who are taking tocilizumab for diseases such as rheumatoid arthritis as well as potentially offer a new drug target for developing anti-obesity medications.

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