Summary
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.
Beschreibung
Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation - ScienceDirect
%0 Journal Article
%1 AGUDELO2018378
%A Agudelo, Leandro Z.
%A Ferreira, Duarte M.S.
%A Cervenka, Igor
%A Bryzgalova, Galyna
%A Dadvar, Shamim
%A Jannig, Paulo R.
%A Pettersson-Klein, Amanda T.
%A Lakshmikanth, Tadepally
%A Sustarsic, Elahu G.
%A Porsmyr-Palmertz, Margareta
%A Correia, Jorge C.
%A Izadi, Manizheh
%A Martínez-Redondo, Vicente
%A Ueland, Per M.
%A Midttun, Øivind
%A Gerhart-Hines, Zachary
%A Brodin, Petter
%A Pereira, Teresa
%A Berggren, Per-Olof
%A Ruas, Jorge L.
%D 2018
%J Cell Metabolism
%K Adipose Inflammation, tissue
%N 2
%P 378 - 392.e5
%R https://doi.org/10.1016/j.cmet.2018.01.004
%T Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation
%U http://www.sciencedirect.com/science/article/pii/S1550413118300536
%V 27
%X Summary
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.
@article{AGUDELO2018378,
abstract = {Summary
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.},
added-at = {2020-04-02T16:06:47.000+0200},
author = {Agudelo, Leandro Z. and Ferreira, Duarte M.S. and Cervenka, Igor and Bryzgalova, Galyna and Dadvar, Shamim and Jannig, Paulo R. and Pettersson-Klein, Amanda T. and Lakshmikanth, Tadepally and Sustarsic, Elahu G. and Porsmyr-Palmertz, Margareta and Correia, Jorge C. and Izadi, Manizheh and Martínez-Redondo, Vicente and Ueland, Per M. and Midttun, Øivind and Gerhart-Hines, Zachary and Brodin, Petter and Pereira, Teresa and Berggren, Per-Olof and Ruas, Jorge L.},
biburl = {https://www.bibsonomy.org/bibtex/231c28b241428daa23118a8b67b4bf8fb/lkanth},
description = {Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation - ScienceDirect},
doi = {https://doi.org/10.1016/j.cmet.2018.01.004},
interhash = {03a76368c857bf2ae8d987f2e9737e9a},
intrahash = {31c28b241428daa23118a8b67b4bf8fb},
issn = {1550-4131},
journal = {Cell Metabolism},
keywords = {Adipose Inflammation, tissue},
number = 2,
pages = {378 - 392.e5},
timestamp = {2020-04-02T16:06:47.000+0200},
title = {Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation},
url = {http://www.sciencedirect.com/science/article/pii/S1550413118300536},
volume = 27,
year = 2018
}