The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. / Klein, Anders B; Nicolaisen, Trine Sand; Johann, Kornelia; Fritzen, Andreas Mæchel; Mathiesen, Cecilie V; Gil, Cláudia; Pilmark, Nanna Skytt; Karstoft, Kristian; Blond, Martin Bæk; Quist, Jonas Salling; Seeley, Randy J; Færch, Kristine; Lund, Jens; Kleinert, Maximilian; Clemmensen, Christoffer.

In: Cell Reports, Vol. 40, No. 8, 111258, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Klein, AB, Nicolaisen, TS, Johann, K, Fritzen, AM, Mathiesen, CV, Gil, C, Pilmark, NS, Karstoft, K, Blond, MB, Quist, JS, Seeley, RJ, Færch, K, Lund, J, Kleinert, M & Clemmensen, C 2022, 'The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance', Cell Reports, vol. 40, no. 8, 111258. https://doi.org/10.1016/j.celrep.2022.111258

APA

Klein, A. B., Nicolaisen, T. S., Johann, K., Fritzen, A. M., Mathiesen, C. V., Gil, C., Pilmark, N. S., Karstoft, K., Blond, M. B., Quist, J. S., Seeley, R. J., Færch, K., Lund, J., Kleinert, M., & Clemmensen, C. (2022). The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. Cell Reports, 40(8), [111258]. https://doi.org/10.1016/j.celrep.2022.111258

Vancouver

Klein AB, Nicolaisen TS, Johann K, Fritzen AM, Mathiesen CV, Gil C et al. The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. Cell Reports. 2022;40(8). 111258. https://doi.org/10.1016/j.celrep.2022.111258

Author

Klein, Anders B ; Nicolaisen, Trine Sand ; Johann, Kornelia ; Fritzen, Andreas Mæchel ; Mathiesen, Cecilie V ; Gil, Cláudia ; Pilmark, Nanna Skytt ; Karstoft, Kristian ; Blond, Martin Bæk ; Quist, Jonas Salling ; Seeley, Randy J ; Færch, Kristine ; Lund, Jens ; Kleinert, Maximilian ; Clemmensen, Christoffer. / The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance. In: Cell Reports. 2022 ; Vol. 40, No. 8.

Bibtex

@article{1e0fcd385c064f758c25c15a2e54e64f,

title = "The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance",

abstract = "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.",

keywords = "Faculty of Science, Metformin, GDF15, Energy balance",

author = "Klein, {Anders B} and Nicolaisen, {Trine Sand} and Kornelia Johann and Fritzen, {Andreas M{\ae}chel} and Mathiesen, {Cecilie V} and Cl{\'a}udia Gil and Pilmark, {Nanna Skytt} and Kristian Karstoft and Blond, {Martin B{\ae}k} and Quist, {Jonas Salling} and Seeley, {Randy J} and Kristine F{\ae}rch and Jens Lund and Maximilian Kleinert and Christoffer Clemmensen",

year = "2022",

doi = "10.1016/j.celrep.2022.111258",

language = "English",

volume = "40",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "8",

}

RIS

TY - JOUR

T1 - The GDF15-GFRAL pathway is dispensable for the effects of metformin on energy balance

AU - Klein, Anders B

AU - Nicolaisen, Trine Sand

AU - Johann, Kornelia

AU - Fritzen, Andreas Mæchel

AU - Mathiesen, Cecilie V

AU - Gil, Cláudia

AU - Pilmark, Nanna Skytt

AU - Karstoft, Kristian

AU - Blond, Martin Bæk

AU - Quist, Jonas Salling

AU - Seeley, Randy J

AU - Færch, Kristine

AU - Lund, Jens

AU - Kleinert, Maximilian

AU - Clemmensen, Christoffer

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Faculty of Science

KW - Metformin

KW - GDF15

KW - Energy balance

U2 - 10.1016/j.celrep.2022.111258

DO - 10.1016/j.celrep.2022.111258

M3 - Journal article

C2 - 36001956

VL - 40

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 8

M1 - 111258

ER -

ID: 317510389