GDF15 increases insulin action in the liver and adipose tissue via a β-adrenergic receptor-mediated mechanism
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GDF15 increases insulin action in the liver and adipose tissue via a β-adrenergic receptor-mediated mechanism. / Sjøberg, Kim Anker; Sigvardsen, Casper Møller; Alvarado-Diaz, Abdiel; Andersen, Nicoline Resen; Larance, Mark; Seeley, Randy J; Schjerling, Peter; Knudsen, Jakob Grunnet; Katzilieris-Petras, Georgios; Clemmensen, Christoffer; Jørgensen, Sebastian Beck; De Bock, Katrien; Richter, Erik A.
I: Cell Metabolism, Bind 35, Nr. 8, 2023, s. 1327-1340.e5.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - GDF15 increases insulin action in the liver and adipose tissue via a β-adrenergic receptor-mediated mechanism
AU - Sjøberg, Kim Anker
AU - Sigvardsen, Casper Møller
AU - Alvarado-Diaz, Abdiel
AU - Andersen, Nicoline Resen
AU - Larance, Mark
AU - Seeley, Randy J
AU - Schjerling, Peter
AU - Knudsen, Jakob Grunnet
AU - Katzilieris-Petras, Georgios
AU - Clemmensen, Christoffer
AU - Jørgensen, Sebastian Beck
AU - De Bock, Katrien
AU - Richter, Erik A.
N1 - Copyright © 2023 Elsevier Inc. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Growth differentiation factor 15 (GDF15) induces weight loss and increases insulin action in obese rodents. Whether and how GDF15 improves insulin action without weight loss is unknown. Obese rats were treated with GDF15 and displayed increased insulin tolerance 5 h later. Lean and obese female and male mice were treated with GDF15 on days 1, 3, and 5 without weight loss and displayed increased insulin sensitivity during a euglycemic hyperinsulinemic clamp on day 6 due to enhanced suppression of endogenous glucose production and increased glucose uptake in WAT and BAT. GDF15 also reduced glucagon levels during clamp independently of the GFRAL receptor. The insulin-sensitizing effect of GDF15 was completely abrogated in GFRAL KO mice and also by treatment with the β-adrenergic antagonist propranolol and in β1,β2-adrenergic receptor KO mice. GDF15 activation of the GFRAL receptor increases β-adrenergic signaling, in turn, improving insulin action in the liver and white and brown adipose tissue.
AB - Growth differentiation factor 15 (GDF15) induces weight loss and increases insulin action in obese rodents. Whether and how GDF15 improves insulin action without weight loss is unknown. Obese rats were treated with GDF15 and displayed increased insulin tolerance 5 h later. Lean and obese female and male mice were treated with GDF15 on days 1, 3, and 5 without weight loss and displayed increased insulin sensitivity during a euglycemic hyperinsulinemic clamp on day 6 due to enhanced suppression of endogenous glucose production and increased glucose uptake in WAT and BAT. GDF15 also reduced glucagon levels during clamp independently of the GFRAL receptor. The insulin-sensitizing effect of GDF15 was completely abrogated in GFRAL KO mice and also by treatment with the β-adrenergic antagonist propranolol and in β1,β2-adrenergic receptor KO mice. GDF15 activation of the GFRAL receptor increases β-adrenergic signaling, in turn, improving insulin action in the liver and white and brown adipose tissue.
KW - Faculty of Science
KW - Insulin sensitivity
KW - Euglycemic clamp
KW - Appetite control
KW - Insulin resistance
KW - Glucose metabolism
KW - GFRAL receptor
KW - Adrenergic receptors
KW - Glucagon
U2 - 10.1016/j.cmet.2023.06.016
DO - 10.1016/j.cmet.2023.06.016
M3 - Journal article
C2 - 37473755
VL - 35
SP - 1327-1340.e5
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 8
ER -
ID: 360706013