Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression

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

Standard

Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. / Agudelo, Leandro Z; Femenía, Teresa; Orhan, Funda; Porsmyr-Palmertz, Margareta; Goiny, Michel; Martinez-Redondo, Vicente; Correia, Jorge C; Izadi, Manizheh; Bhat, Maria; Schuppe-Koistinen, Ina; Pettersson, Amanda T; Ferreira, Duarte M S; Krook, Anna; Barres, Romain; Zierath, Juleen R; Erhardt, Sophie; Lindskog, Maria; Ruas, Jorge L.

In: Cell, Vol. 159, No. 1, 25.09.2014, p. 33-45.

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

Harvard

Agudelo, LZ, Femenía, T, Orhan, F, Porsmyr-Palmertz, M, Goiny, M, Martinez-Redondo, V, Correia, JC, Izadi, M, Bhat, M, Schuppe-Koistinen, I, Pettersson, AT, Ferreira, DMS, Krook, A, Barres, R, Zierath, JR, Erhardt, S, Lindskog, M & Ruas, JL 2014, 'Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression', Cell, vol. 159, no. 1, pp. 33-45. https://doi.org/10.1016/j.cell.2014.07.051

APA

Agudelo, L. Z., Femenía, T., Orhan, F., Porsmyr-Palmertz, M., Goiny, M., Martinez-Redondo, V., Correia, J. C., Izadi, M., Bhat, M., Schuppe-Koistinen, I., Pettersson, A. T., Ferreira, D. M. S., Krook, A., Barres, R., Zierath, J. R., Erhardt, S., Lindskog, M., & Ruas, J. L. (2014). Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell, 159(1), 33-45. https://doi.org/10.1016/j.cell.2014.07.051

Vancouver

Agudelo LZ, Femenía T, Orhan F, Porsmyr-Palmertz M, Goiny M, Martinez-Redondo V et al. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell. 2014 Sep 25;159(1):33-45. https://doi.org/10.1016/j.cell.2014.07.051

Author

Agudelo, Leandro Z ; Femenía, Teresa ; Orhan, Funda ; Porsmyr-Palmertz, Margareta ; Goiny, Michel ; Martinez-Redondo, Vicente ; Correia, Jorge C ; Izadi, Manizheh ; Bhat, Maria ; Schuppe-Koistinen, Ina ; Pettersson, Amanda T ; Ferreira, Duarte M S ; Krook, Anna ; Barres, Romain ; Zierath, Juleen R ; Erhardt, Sophie ; Lindskog, Maria ; Ruas, Jorge L. / Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. In: Cell. 2014 ; Vol. 159, No. 1. pp. 33-45.

Bibtex

@article{b5c6f5e064094bd086a730e49a791af0,
title = "Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression",
abstract = "Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which skeletal muscle PGC-1α1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1α1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration. This study opens therapeutic avenues for the treatment of depression by targeting the PGC-1α1-PPAR axis in skeletal muscle, without the need to cross the blood-brain barrier.",
keywords = "Animals, Blood-Brain Barrier, Depression, Gene Expression Profiling, Humans, Kynurenic Acid, Kynurenine, Mice, Muscle Fibers, Skeletal, Muscle, Skeletal, PPAR alpha, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Physical Conditioning, Animal, Physical Conditioning, Human, Stress, Psychological, Transaminases, Transcription Factors, Journal Article, Research Support, Non-U.S. Gov't",
author = "Agudelo, {Leandro Z} and Teresa Femen{\'i}a and Funda Orhan and Margareta Porsmyr-Palmertz and Michel Goiny and Vicente Martinez-Redondo and Correia, {Jorge C} and Manizheh Izadi and Maria Bhat and Ina Schuppe-Koistinen and Pettersson, {Amanda T} and Ferreira, {Duarte M S} and Anna Krook and Romain Barres and Zierath, {Juleen R} and Sophie Erhardt and Maria Lindskog and Ruas, {Jorge L}",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2014",
month = sep,
day = "25",
doi = "10.1016/j.cell.2014.07.051",
language = "English",
volume = "159",
pages = "33--45",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression

AU - Agudelo, Leandro Z

AU - Femenía, Teresa

AU - Orhan, Funda

AU - Porsmyr-Palmertz, Margareta

AU - Goiny, Michel

AU - Martinez-Redondo, Vicente

AU - Correia, Jorge C

AU - Izadi, Manizheh

AU - Bhat, Maria

AU - Schuppe-Koistinen, Ina

AU - Pettersson, Amanda T

AU - Ferreira, Duarte M S

AU - Krook, Anna

AU - Barres, Romain

AU - Zierath, Juleen R

AU - Erhardt, Sophie

AU - Lindskog, Maria

AU - Ruas, Jorge L

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/9/25

Y1 - 2014/9/25

N2 - Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which skeletal muscle PGC-1α1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1α1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration. This study opens therapeutic avenues for the treatment of depression by targeting the PGC-1α1-PPAR axis in skeletal muscle, without the need to cross the blood-brain barrier.

AB - Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which skeletal muscle PGC-1α1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1α1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration. This study opens therapeutic avenues for the treatment of depression by targeting the PGC-1α1-PPAR axis in skeletal muscle, without the need to cross the blood-brain barrier.

KW - Animals

KW - Blood-Brain Barrier

KW - Depression

KW - Gene Expression Profiling

KW - Humans

KW - Kynurenic Acid

KW - Kynurenine

KW - Mice

KW - Muscle Fibers, Skeletal

KW - Muscle, Skeletal

KW - PPAR alpha

KW - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

KW - Physical Conditioning, Animal

KW - Physical Conditioning, Human

KW - Stress, Psychological

KW - Transaminases

KW - Transcription Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.cell.2014.07.051

DO - 10.1016/j.cell.2014.07.051

M3 - Journal article

C2 - 25259918

VL - 159

SP - 33

EP - 45

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -

ID: 172479176