AI Article Synopsis
- - GDF15 treatment in obese rats led to improved insulin tolerance within hours, suggesting a rapid effect on insulin action regardless of weight loss.
- - Male and female mice receiving GDF15 showed increased insulin sensitivity without weight loss, attributed to reduced glucose production and enhanced uptake in fat tissues.
- - The insulin-sensitizing effects of GDF15 were eliminated in mice lacking the GFRAL receptor and through β-adrenergic blockers, indicating that GDF15 works via the GFRAL receptor to boost β-adrenergic signaling for better insulin function.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.cmet.2023.06.016 | DOI Listing |
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