The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance
Research output: Contribution to journal › Journal article › peer-review
- Klein et al_Cell Reports_2022_Vol 40(8)_e111258
Final published version, 2.49 MB, PDF document
Metformin is a blood-glucose-lowering medication with physiological effects that extend beyond its anti-diabetic indication. Recently, it was reported that metformin lowers body weight via induction of growth differentiation factor 15 (GDF15), which suppresses food intake by binding to the GDNF family receptor α-like (GFRAL) in the hindbrain. Here, we corroborate that metformin increases circulating GDF15 in mice and humans, but we fail to confirm previous reports that the GDF15-GFRAL pathway is necessary for the weight-lowering effects of metformin. Instead, our studies in wild-type, GDF15 knockout, and GFRAL knockout mice suggest that the GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. The data presented here question whether metformin is a sufficiently strong stimulator of GDF15 to drive anorexia and weight loss and emphasize that additional work is needed to untangle the relationship among metformin, GDF15, and energy balance.
|Publication status||Published - 2022|
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
- Faculty of Science - Metformin, GDF15, Energy balance