Influence of Obesity and IL-6 on Human Postprandial Amino Acid and Protein Metabolism at Whole-body and Tissue Level

Abstract

Context: Sarcopenic obesity, the loss of muscle mass and function in people with obesity, may result from altered muscle protein synthesis and degradation. Chronic low-grade inflammation, particularly IL-6, has been implicated. Objective: To assess the role of IL-6 in protein and amino acid metabolism during fasting and postprandial states in humans with healthy weight or obesity at whole-body, skeletal muscle, and subcutaneous adipose tissue levels. Methods: In this placebo-controlled, nonrandomized, participant-blinded study, 12 men with healthy weight and 12 men with obesity received placebo (0.9% saline) or 3 weeks of IL-6 receptor blockade with tocilizumab. Isotope dilution/incorporation techniques and arteriovenous balance measurements were applied in fasted and postprandial states. The trial was originally designed to examine IL-6 effects on fat storage (reported previously). Here, we present prespecified exploratory outcomes on amino acid and protein turnover. Results: Obesity was associated with reduced meal-induced muscle-protein gain driven by impaired suppression of muscle protein degradation, and with reduced appearance of amino acids from meals. In both groups, IL-6 receptor blockade increased fasting and postprandial plasma amino acids and reduced postprandial plasma protein synthesis without affecting skeletal muscle protein turnover. In the healthy weight group, it also increased amino acid appearance from the meal and postprandial phenylalanine oxidation. Conclusion: Obesity impairs meal-induced muscle-protein gain, through insufficient suppression of protein degradation. Basal IL-6 activity does not regulate muscle protein turnover but influences amino acid metabolism and protein synthesis in extramuscular tissues.