Trinh · Cell reports. Medicine 2021 · non-randomized, participant-blinded, placebo-controlled crossover trial · n=?

Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men.

Cited 42 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized, placebo-controlled crossover clinical trial

PubMed 34622233 · doi:10.1016/j.xcrm.2021.100396 · record verified 2026-08-29

What was done

In a placebo-controlled, non-randomized, participant-blinded crossover study, researchers administered the IL-6 receptor antagonist tocilizumab or placebo to lean and obese men. They evaluated systemic energy metabolism, free fatty acid appearance, lipolysis (glycerol appearance rate), fatty acid oxidation, and glucose kinetics during rest, exercise, and recovery using tracer dilution methodology.

What was found

The abstract reports directional findings without numerical values or statistical estimates. Tocilizumab reduced circulating fatty acid appearance across rest, exercise, and recovery in both lean and obese participants. Lipolysis (rate of glycerol appearance), fatty acid oxidation, and glucose kinetics were not meaningfully altered, indicating that reduced fatty acid availability was driven by increased fatty acid re-esterification rather than suppressed triglyceride breakdown.

Why it matters

This study identifies a physiological role for endogenous IL-6 in regulating fatty acid mobilization in humans, offering a potential metabolic mechanism for the adipose tissue expansion and weight gain reported with therapeutic IL-6 inhibition.

Limits

The trial was non-randomized, restricted to male participants, and the abstract omits sample size, participant baseline characteristics, and exact quantitative data with confidence intervals. Long-term metabolic and body composition changes were not assessed.

Cited by