Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Anthony J. Covarrubias; Halil Ibrahim Aksoylar; Jiujiu Yu; Nathaniel W. Snyder; Andrew J. Worth; Shankar S. Iyer; Jiawei Wang; Issam Ben-Sahra; Vanessa Byles; Tiffany Polynne-Stapornkul; Erika C. Espinosa; Dudley Lamming; Brendan D. Manning; Yijing Zhang; Ian A. Blair; Tiffany Horng

doi:10.7554/eLife.11612

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Anthony J. Covarrubias, Halil Ibrahim Aksoylar, Jiujiu Yu, Nathaniel W. Snyder, Andrew J. Worth, Shankar S. Iyer, Jiawei Wang, Issam Ben-Sahra, Vanessa Byles, Tiffany Polynne-Stapornkul, Erika C. Espinosa, Dudley Lamming, Brendan D. Manning, Yijing Zhang, Ian A. Blair, Tiffany Horng^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

337 Scopus citations

Abstract

Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.

Original language	English (US)
Article number	e11612
Journal	eLife
Volume	5
Issue number	FEBRUARY2016
DOIs	https://doi.org/10.7554/eLife.11612
State	Published - Feb 19 2016

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

Access to Document

10.7554/eLife.11612

Cite this

Covarrubias, A. J., Aksoylar, H. I., Yu, J., Snyder, N. W., Worth, A. J., Iyer, S. S., Wang, J., Ben-Sahra, I., Byles, V., Polynne-Stapornkul, T., Espinosa, E. C., Lamming, D., Manning, B. D., Zhang, Y., Blair, I. A., & Horng, T. (2016). Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation. eLife, 5(FEBRUARY2016), Article e11612. https://doi.org/10.7554/eLife.11612

@article{4a21cf58215e43cc99b2286554525d39,

title = "Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation",

abstract = "Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.",

author = "Covarrubias, {Anthony J.} and Aksoylar, {Halil Ibrahim} and Jiujiu Yu and Snyder, {Nathaniel W.} and Worth, {Andrew J.} and Iyer, {Shankar S.} and Jiawei Wang and Issam Ben-Sahra and Vanessa Byles and Tiffany Polynne-Stapornkul and Espinosa, {Erika C.} and Dudley Lamming and Manning, {Brendan D.} and Yijing Zhang and Blair, {Ian A.} and Tiffany Horng",

note = "Publisher Copyright: {\textcopyright} Covarrubias et al.",

year = "2016",

month = feb,

day = "19",

doi = "10.7554/eLife.11612",

language = "English (US)",

volume = "5",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

number = "FEBRUARY2016",

}

Covarrubias, AJ, Aksoylar, HI, Yu, J, Snyder, NW, Worth, AJ, Iyer, SS, Wang, J, Ben-Sahra, I, Byles, V, Polynne-Stapornkul, T, Espinosa, EC, Lamming, D, Manning, BD, Zhang, Y, Blair, IA & Horng, T 2016, 'Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation', eLife, vol. 5, no. FEBRUARY2016, e11612. https://doi.org/10.7554/eLife.11612

TY - JOUR

T1 - Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

AU - Covarrubias, Anthony J.

AU - Aksoylar, Halil Ibrahim

AU - Yu, Jiujiu

AU - Snyder, Nathaniel W.

AU - Worth, Andrew J.

AU - Iyer, Shankar S.

AU - Wang, Jiawei

AU - Ben-Sahra, Issam

AU - Byles, Vanessa

AU - Polynne-Stapornkul, Tiffany

AU - Espinosa, Erika C.

AU - Lamming, Dudley

AU - Manning, Brendan D.

AU - Zhang, Yijing

AU - Blair, Ian A.

AU - Horng, Tiffany

PY - 2016/2/19

Y1 - 2016/2/19

N2 - Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.

AB - Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.

UR - http://www.scopus.com/inward/record.url?scp=84961281785&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961281785&partnerID=8YFLogxK

U2 - 10.7554/eLife.11612

DO - 10.7554/eLife.11612

M3 - Article

C2 - 26894960

AN - SCOPUS:84961281785

SN - 2050-084X

VL - 5

JO - eLife

JF - eLife

IS - FEBRUARY2016

M1 - e11612

ER -

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this