Lacking IL-6 signaling leads to an expansion of adipose tissue mass in rodents and humans. However, the underlying mechanisms have not been identified.This project aims to investigate the overall hypothesis that IL-6 receptor blockade changes substrate metabolism during postabsorptive and postprandial states to favor storage over mobilization of fat and to favor glucose over fat as a source for energy production. This hypothesis finds some support in the literature: Infusion of recombinant IL-6 into humans, leading to high concentrations of IL-6 in the circulation, stimulates lipolysis and free fatty acid oxidation.~Therefore, the investigators hypothesize that IL-6 receptor blockade impairs the mobilization of FFA from adipose tissue and impairs fat oxidation in skeletal muscle in the postabsorptive state. In the postprandial, state the investigators hypothesize that IL-6 receptor blockade reduces the insulin-induced uptake and deposition of fat by adipose tissue and skeletal muscle, therefore contributing to ectopic fat deposition in the liver.~In this study 12 lean and 12 obese male participants will be included. The participants will attend one screening visit and two study visits. The IL-6 receptor antibody tocilizumab will be infused on study visit 1.~Isotope dilution techniques, blood flow measurements, arterio-venous differences across adipose tissue and skeletal muscle, fat and skeletal muscle biopsies will be used to assess lipid, glucose and protein kinetics on a whole-body as well as fat and skeletal muscle level in the fasting state and after the ingestion of a liquid mixed-meal. Respiratory exchange ratio will be measured by indirect calorimetry.
The overall purpose of this explorative yet quantitative study project is to understand how blocking IL-6 signaling leads to the expansion of adipose tissue mass in humans in vivo. The aim is to gain in depth knowledge about how IL-6 receptor blockade affects human lipid, glucose and protein metabolism, specifically the uptake and storage of substrates from a meal vs. their utilization, hence the balance determining whether one gains or loses fat mass.