Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

Research output: Contribution to journalJournal articlepeer-review

Standard

Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis. / Sveidahl Johansen, Olivia; Ma, Tao; Hansen, Jakob Bondo; Markussen, Lasse Kruse; Schreiber, Renate; Reverte-Salisa, Laia; Dong, Hua; Christensen, Dan Ploug; Sun, Wenfei; Gnad, Thorsten; Karavaeva, Iuliia; Nielsen, Thomas Svava; Kooijman, Sander; Cero, Cheryl; Dmytriyeva, Oksana; Shen, Yachen; Razzoli, Maria; O'Brien, Shannon L; Kuipers, Eline N; Nielsen, Carsten Haagen; Orchard, William; Willemsen, Nienke; Jespersen, Naja Zenius; Lundh, Morten; Sustarsic, Elahu Gosney; Hallgren, Cecilie Mørch; Frost, Mikkel; McGonigle, Seth; Isidor, Marie Sophie; Broholm, Christa; Pedersen, Oluf; Hansen, Jacob Bo; Grarup, Niels; Hansen, Torben; Kjær, Andreas; Granneman, James G; Babu, M Madan; Calebiro, Davide; Nielsen, Søren; Rydén, Mikael; Soccio, Raymond; Rensen, Patrick C N; Treebak, Jonas Thue; Schwartz, Thue Walter; Emanuelli, Brice; Bartolomucci, Alessandro; Pfeifer, Alexander; Zechner, Rudolf; Scheele, Camilla; Mandrup, Susanne; Gerhart-Hines, Zachary.

In: Cell, Vol. 184, No. 13, 2021, p. 3502-3518 +.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Sveidahl Johansen, O, Ma, T, Hansen, JB, Markussen, LK, Schreiber, R, Reverte-Salisa, L, Dong, H, Christensen, DP, Sun, W, Gnad, T, Karavaeva, I, Nielsen, TS, Kooijman, S, Cero, C, Dmytriyeva, O, Shen, Y, Razzoli, M, O'Brien, SL, Kuipers, EN, Nielsen, CH, Orchard, W, Willemsen, N, Jespersen, NZ, Lundh, M, Sustarsic, EG, Hallgren, CM, Frost, M, McGonigle, S, Isidor, MS, Broholm, C, Pedersen, O, Hansen, JB, Grarup, N, Hansen, T, Kjær, A, Granneman, JG, Babu, MM, Calebiro, D, Nielsen, S, Rydén, M, Soccio, R, Rensen, PCN, Treebak, JT, Schwartz, TW, Emanuelli, B, Bartolomucci, A, Pfeifer, A, Zechner, R, Scheele, C, Mandrup, S & Gerhart-Hines, Z 2021, 'Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis', Cell, vol. 184, no. 13, pp. 3502-3518 +. https://doi.org/10.1016/j.cell.2021.04.037

APA

Sveidahl Johansen, O., Ma, T., Hansen, J. B., Markussen, L. K., Schreiber, R., Reverte-Salisa, L., Dong, H., Christensen, D. P., Sun, W., Gnad, T., Karavaeva, I., Nielsen, T. S., Kooijman, S., Cero, C., Dmytriyeva, O., Shen, Y., Razzoli, M., O'Brien, S. L., Kuipers, E. N., ... Gerhart-Hines, Z. (2021). Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis. Cell, 184(13), 3502-3518 +. https://doi.org/10.1016/j.cell.2021.04.037

Vancouver

Sveidahl Johansen O, Ma T, Hansen JB, Markussen LK, Schreiber R, Reverte-Salisa L et al. Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis. Cell. 2021;184(13):3502-3518 +. https://doi.org/10.1016/j.cell.2021.04.037

Author

Sveidahl Johansen, Olivia ; Ma, Tao ; Hansen, Jakob Bondo ; Markussen, Lasse Kruse ; Schreiber, Renate ; Reverte-Salisa, Laia ; Dong, Hua ; Christensen, Dan Ploug ; Sun, Wenfei ; Gnad, Thorsten ; Karavaeva, Iuliia ; Nielsen, Thomas Svava ; Kooijman, Sander ; Cero, Cheryl ; Dmytriyeva, Oksana ; Shen, Yachen ; Razzoli, Maria ; O'Brien, Shannon L ; Kuipers, Eline N ; Nielsen, Carsten Haagen ; Orchard, William ; Willemsen, Nienke ; Jespersen, Naja Zenius ; Lundh, Morten ; Sustarsic, Elahu Gosney ; Hallgren, Cecilie Mørch ; Frost, Mikkel ; McGonigle, Seth ; Isidor, Marie Sophie ; Broholm, Christa ; Pedersen, Oluf ; Hansen, Jacob Bo ; Grarup, Niels ; Hansen, Torben ; Kjær, Andreas ; Granneman, James G ; Babu, M Madan ; Calebiro, Davide ; Nielsen, Søren ; Rydén, Mikael ; Soccio, Raymond ; Rensen, Patrick C N ; Treebak, Jonas Thue ; Schwartz, Thue Walter ; Emanuelli, Brice ; Bartolomucci, Alessandro ; Pfeifer, Alexander ; Zechner, Rudolf ; Scheele, Camilla ; Mandrup, Susanne ; Gerhart-Hines, Zachary. / Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis. In: Cell. 2021 ; Vol. 184, No. 13. pp. 3502-3518 +.

Bibtex

@article{2005e53e6a6147008d833768763ace97,
title = "Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis",
abstract = "Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of β-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gs-coupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.",
author = "{Sveidahl Johansen}, Olivia and Tao Ma and Hansen, {Jakob Bondo} and Markussen, {Lasse Kruse} and Renate Schreiber and Laia Reverte-Salisa and Hua Dong and Christensen, {Dan Ploug} and Wenfei Sun and Thorsten Gnad and Iuliia Karavaeva and Nielsen, {Thomas Svava} and Sander Kooijman and Cheryl Cero and Oksana Dmytriyeva and Yachen Shen and Maria Razzoli and O'Brien, {Shannon L} and Kuipers, {Eline N} and Nielsen, {Carsten Haagen} and William Orchard and Nienke Willemsen and Jespersen, {Naja Zenius} and Morten Lundh and Sustarsic, {Elahu Gosney} and Hallgren, {Cecilie M{\o}rch} and Mikkel Frost and Seth McGonigle and Isidor, {Marie Sophie} and Christa Broholm and Oluf Pedersen and Hansen, {Jacob Bo} and Niels Grarup and Torben Hansen and Andreas Kj{\ae}r and Granneman, {James G} and Babu, {M Madan} and Davide Calebiro and S{\o}ren Nielsen and Mikael Ryd{\'e}n and Raymond Soccio and Rensen, {Patrick C N} and Treebak, {Jonas Thue} and Schwartz, {Thue Walter} and Brice Emanuelli and Alessandro Bartolomucci and Alexander Pfeifer and Rudolf Zechner and Camilla Scheele and Susanne Mandrup and Zachary Gerhart-Hines",
note = "Copyright {\textcopyright} 2021 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2021",
doi = "10.1016/j.cell.2021.04.037",
language = "English",
volume = "184",
pages = "3502--3518 +",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "13",

}

RIS

TY - JOUR

T1 - Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

AU - Sveidahl Johansen, Olivia

AU - Ma, Tao

AU - Hansen, Jakob Bondo

AU - Markussen, Lasse Kruse

AU - Schreiber, Renate

AU - Reverte-Salisa, Laia

AU - Dong, Hua

AU - Christensen, Dan Ploug

AU - Sun, Wenfei

AU - Gnad, Thorsten

AU - Karavaeva, Iuliia

AU - Nielsen, Thomas Svava

AU - Kooijman, Sander

AU - Cero, Cheryl

AU - Dmytriyeva, Oksana

AU - Shen, Yachen

AU - Razzoli, Maria

AU - O'Brien, Shannon L

AU - Kuipers, Eline N

AU - Nielsen, Carsten Haagen

AU - Orchard, William

AU - Willemsen, Nienke

AU - Jespersen, Naja Zenius

AU - Lundh, Morten

AU - Sustarsic, Elahu Gosney

AU - Hallgren, Cecilie Mørch

AU - Frost, Mikkel

AU - McGonigle, Seth

AU - Isidor, Marie Sophie

AU - Broholm, Christa

AU - Pedersen, Oluf

AU - Hansen, Jacob Bo

AU - Grarup, Niels

AU - Hansen, Torben

AU - Kjær, Andreas

AU - Granneman, James G

AU - Babu, M Madan

AU - Calebiro, Davide

AU - Nielsen, Søren

AU - Rydén, Mikael

AU - Soccio, Raymond

AU - Rensen, Patrick C N

AU - Treebak, Jonas Thue

AU - Schwartz, Thue Walter

AU - Emanuelli, Brice

AU - Bartolomucci, Alessandro

AU - Pfeifer, Alexander

AU - Zechner, Rudolf

AU - Scheele, Camilla

AU - Mandrup, Susanne

AU - Gerhart-Hines, Zachary

N1 - Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2021

Y1 - 2021

N2 - Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of β-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gs-coupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.

AB - Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of β-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gs-coupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.

U2 - 10.1016/j.cell.2021.04.037

DO - 10.1016/j.cell.2021.04.037

M3 - Journal article

C2 - 34048700

VL - 184

SP - 3502-3518 +

JO - Cell

JF - Cell

SN - 0092-8674

IS - 13

ER -

ID: 271986976