Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation

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

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Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation. / Agudelo, Leandro Z; Ferreira, Duarte M S; Cervenka, Igor; Bryzgalova, Galyna; Dadvar, Shamim; Jannig, Paulo R; Pettersson-Klein, Amanda T; Lakshmikanth, Tadepally; Sustarsic, Elahu G; Porsmyr-Palmertz, Margareta; Correia, Jorge C; Izadi, Manizheh; Martínez-Redondo, Vicente; Ueland, Per M; Midttun, Øivind; Gerhart-Hines, Zachary; Brodin, Petter; Pereira, Teresa; Berggren, Per-Olof; Ruas, Jorge L.

In: Cell Metabolism, Vol. 27, No. 2, 06.02.2018, p. 378-392.e5.

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

Harvard

Agudelo, LZ, Ferreira, DMS, Cervenka, I, Bryzgalova, G, Dadvar, S, Jannig, PR, Pettersson-Klein, AT, Lakshmikanth, T, Sustarsic, EG, Porsmyr-Palmertz, M, Correia, JC, Izadi, M, Martínez-Redondo, V, Ueland, PM, Midttun, Ø, Gerhart-Hines, Z, Brodin, P, Pereira, T, Berggren, P-O & Ruas, JL 2018, 'Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation', Cell Metabolism, vol. 27, no. 2, pp. 378-392.e5. https://doi.org/10.1016/j.cmet.2018.01.004

APA

Agudelo, L. Z., Ferreira, D. M. S., Cervenka, I., Bryzgalova, G., Dadvar, S., Jannig, P. R., Pettersson-Klein, A. T., Lakshmikanth, T., Sustarsic, E. G., Porsmyr-Palmertz, M., Correia, J. C., Izadi, M., Martínez-Redondo, V., Ueland, P. M., Midttun, Ø., Gerhart-Hines, Z., Brodin, P., Pereira, T., Berggren, P-O., & Ruas, J. L. (2018). Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation. Cell Metabolism, 27(2), 378-392.e5. https://doi.org/10.1016/j.cmet.2018.01.004

Vancouver

Agudelo LZ, Ferreira DMS, Cervenka I, Bryzgalova G, Dadvar S, Jannig PR et al. Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation. Cell Metabolism. 2018 Feb 6;27(2):378-392.e5. https://doi.org/10.1016/j.cmet.2018.01.004

Author

Agudelo, Leandro Z ; Ferreira, Duarte M S ; Cervenka, Igor ; Bryzgalova, Galyna ; Dadvar, Shamim ; Jannig, Paulo R ; Pettersson-Klein, Amanda T ; Lakshmikanth, Tadepally ; Sustarsic, Elahu G ; Porsmyr-Palmertz, Margareta ; Correia, Jorge C ; Izadi, Manizheh ; Martínez-Redondo, Vicente ; Ueland, Per M ; Midttun, Øivind ; Gerhart-Hines, Zachary ; Brodin, Petter ; Pereira, Teresa ; Berggren, Per-Olof ; Ruas, Jorge L. / Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation. In: Cell Metabolism. 2018 ; Vol. 27, No. 2. pp. 378-392.e5.

Bibtex

@article{0752ddec6a6e4ab88a1298ba7e6af2ad,
title = "Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation",
abstract = "The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling. Conversely, genetic deletion of Gpr35 causes progressive weight gain and glucose intolerance, and sensitizes to the effects of high-fat diets. Finally, exercise-induced adipose tissue browning is compromised in Gpr35 knockout animals. This work uncovers kynurenine metabolism as a pathway with therapeutic potential to control energy homeostasis.",
keywords = "Journal Article",
author = "Agudelo, {Leandro Z} and Ferreira, {Duarte M S} and Igor Cervenka and Galyna Bryzgalova and Shamim Dadvar and Jannig, {Paulo R} and Pettersson-Klein, {Amanda T} and Tadepally Lakshmikanth and Sustarsic, {Elahu G} and Margareta Porsmyr-Palmertz and Correia, {Jorge C} and Manizheh Izadi and Vicente Mart{\'i}nez-Redondo and Ueland, {Per M} and {\O}ivind Midttun and Zachary Gerhart-Hines and Petter Brodin and Teresa Pereira and Per-Olof Berggren and Ruas, {Jorge L}",
note = "Copyright {\textcopyright} 2018 Elsevier Inc. All rights reserved.",
year = "2018",
month = feb,
day = "6",
doi = "10.1016/j.cmet.2018.01.004",
language = "English",
volume = "27",
pages = "378--392.e5",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation

AU - Agudelo, Leandro Z

AU - Ferreira, Duarte M S

AU - Cervenka, Igor

AU - Bryzgalova, Galyna

AU - Dadvar, Shamim

AU - Jannig, Paulo R

AU - Pettersson-Klein, Amanda T

AU - Lakshmikanth, Tadepally

AU - Sustarsic, Elahu G

AU - Porsmyr-Palmertz, Margareta

AU - Correia, Jorge C

AU - Izadi, Manizheh

AU - Martínez-Redondo, Vicente

AU - Ueland, Per M

AU - Midttun, Øivind

AU - Gerhart-Hines, Zachary

AU - Brodin, Petter

AU - Pereira, Teresa

AU - Berggren, Per-Olof

AU - Ruas, Jorge L

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/2/6

Y1 - 2018/2/6

N2 - The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling. Conversely, genetic deletion of Gpr35 causes progressive weight gain and glucose intolerance, and sensitizes to the effects of high-fat diets. Finally, exercise-induced adipose tissue browning is compromised in Gpr35 knockout animals. This work uncovers kynurenine metabolism as a pathway with therapeutic potential to control energy homeostasis.

AB - The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. This suppresses weight gain in animals fed a high-fat diet and improves glucose tolerance. Kynurenic acid and Gpr35 enhance Pgc-1α1 expression and cellular respiration, and increase the levels of Rgs14 in adipocytes, which leads to enhanced beta-adrenergic receptor signaling. Conversely, genetic deletion of Gpr35 causes progressive weight gain and glucose intolerance, and sensitizes to the effects of high-fat diets. Finally, exercise-induced adipose tissue browning is compromised in Gpr35 knockout animals. This work uncovers kynurenine metabolism as a pathway with therapeutic potential to control energy homeostasis.

KW - Journal Article

U2 - 10.1016/j.cmet.2018.01.004

DO - 10.1016/j.cmet.2018.01.004

M3 - Journal article

C2 - 29414686

VL - 27

SP - 378-392.e5

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 2

ER -

ID: 189764777