Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men
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Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men. / Trinh, Beckey; Peletier, Merel; Simonsen, Casper; Plomgaard, Peter; Karstoft, Kristian; Klarlund Pedersen, Bente; van Hall, Gerrit; Ellingsgaard, Helga.
I: Cell Reports Medicine, Bind 2, Nr. 9, 100396, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men
AU - Trinh, Beckey
AU - Peletier, Merel
AU - Simonsen, Casper
AU - Plomgaard, Peter
AU - Karstoft, Kristian
AU - Klarlund Pedersen, Bente
AU - van Hall, Gerrit
AU - Ellingsgaard, Helga
N1 - Publisher Copyright: © 2021 The Authors
PY - 2021
Y1 - 2021
N2 - Lack of interleukin-6 (IL-6) leads to expansion of adipose tissue mass in rodents and humans. The exact underlying mechanisms have not been identified. In this placebo-controlled, non-randomized, participant-blinded crossover study, we use the IL-6 receptor antibody tocilizumab to investigate the role of endogenous IL-6 in regulating systemic energy metabolism at rest and during exercise and recovery in lean and obese men using tracer dilution methodology. Tocilizumab reduces fatty acid appearance in the circulation under all conditions in lean and obese individuals, whereas lipolysis (the rate of glycerol appearance into the circulation) is mostly unaffected. The fact that fatty acid oxidation is unaffected by IL-6 receptor blockade suggests increased re-esterification of fatty acids. Glucose kinetics are unaffected. We find that blocking endogenous IL-6 signaling with tocilizumab impairs fat mobilization, which may contribute to expansion of adipose tissue mass and, thus, affect the health of individuals undergoing anti-IL-6 therapy (Clinicaltrials.gov: NCT03967691).
AB - Lack of interleukin-6 (IL-6) leads to expansion of adipose tissue mass in rodents and humans. The exact underlying mechanisms have not been identified. In this placebo-controlled, non-randomized, participant-blinded crossover study, we use the IL-6 receptor antibody tocilizumab to investigate the role of endogenous IL-6 in regulating systemic energy metabolism at rest and during exercise and recovery in lean and obese men using tracer dilution methodology. Tocilizumab reduces fatty acid appearance in the circulation under all conditions in lean and obese individuals, whereas lipolysis (the rate of glycerol appearance into the circulation) is mostly unaffected. The fact that fatty acid oxidation is unaffected by IL-6 receptor blockade suggests increased re-esterification of fatty acids. Glucose kinetics are unaffected. We find that blocking endogenous IL-6 signaling with tocilizumab impairs fat mobilization, which may contribute to expansion of adipose tissue mass and, thus, affect the health of individuals undergoing anti-IL-6 therapy (Clinicaltrials.gov: NCT03967691).
KW - exercise
KW - fatty acids
KW - glycerol
KW - IL-6 receptor
KW - Interleukin-6
KW - lipolysis
KW - metabolism
KW - obesity
KW - stable isotopes
KW - tocilizumab
U2 - 10.1016/j.xcrm.2021.100396
DO - 10.1016/j.xcrm.2021.100396
M3 - Journal article
C2 - 34622233
AN - SCOPUS:85115410406
VL - 2
JO - Cell Reports Medicine
JF - Cell Reports Medicine
SN - 2666-3791
IS - 9
M1 - 100396
ER -
ID: 281160353