Lipolysis regulates major transcriptional programs in brown adipocytes

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

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Lipolysis regulates major transcriptional programs in brown adipocytes. / Markussen, Lasse K.; Rondini, Elizabeth A.; Johansen, Olivia Sveidahl; Madsen, Jesper G.S.; Sustarsic, Elahu G.; Marcher, Ann Britt; Hansen, Jacob B.; Gerhart-Hines, Zachary; Granneman, James G.; Mandrup, Susanne.

In: Nature Communications, Vol. 13, No. 1, 3956, 2022.

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

Harvard

Markussen, LK, Rondini, EA, Johansen, OS, Madsen, JGS, Sustarsic, EG, Marcher, AB, Hansen, JB, Gerhart-Hines, Z, Granneman, JG & Mandrup, S 2022, 'Lipolysis regulates major transcriptional programs in brown adipocytes', Nature Communications, vol. 13, no. 1, 3956. https://doi.org/10.1038/s41467-022-31525-8

APA

Markussen, L. K., Rondini, E. A., Johansen, O. S., Madsen, J. G. S., Sustarsic, E. G., Marcher, A. B., Hansen, J. B., Gerhart-Hines, Z., Granneman, J. G., & Mandrup, S. (2022). Lipolysis regulates major transcriptional programs in brown adipocytes. Nature Communications, 13(1), [3956]. https://doi.org/10.1038/s41467-022-31525-8

Vancouver

Markussen LK, Rondini EA, Johansen OS, Madsen JGS, Sustarsic EG, Marcher AB et al. Lipolysis regulates major transcriptional programs in brown adipocytes. Nature Communications. 2022;13(1). 3956. https://doi.org/10.1038/s41467-022-31525-8

Author

Markussen, Lasse K. ; Rondini, Elizabeth A. ; Johansen, Olivia Sveidahl ; Madsen, Jesper G.S. ; Sustarsic, Elahu G. ; Marcher, Ann Britt ; Hansen, Jacob B. ; Gerhart-Hines, Zachary ; Granneman, James G. ; Mandrup, Susanne. / Lipolysis regulates major transcriptional programs in brown adipocytes. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{8688a06940474542868432157796bcec,
title = "Lipolysis regulates major transcriptional programs in brown adipocytes",
abstract = "β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. We have used pharmacological inhibitors and a direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in cultured brown adipocytes. Here we show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, however, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on transcription and function of cultured brown adipocytes.",
author = "Markussen, {Lasse K.} and Rondini, {Elizabeth A.} and Johansen, {Olivia Sveidahl} and Madsen, {Jesper G.S.} and Sustarsic, {Elahu G.} and Marcher, {Ann Britt} and Hansen, {Jacob B.} and Zachary Gerhart-Hines and Granneman, {James G.} and Susanne Mandrup",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-31525-8",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Lipolysis regulates major transcriptional programs in brown adipocytes

AU - Markussen, Lasse K.

AU - Rondini, Elizabeth A.

AU - Johansen, Olivia Sveidahl

AU - Madsen, Jesper G.S.

AU - Sustarsic, Elahu G.

AU - Marcher, Ann Britt

AU - Hansen, Jacob B.

AU - Gerhart-Hines, Zachary

AU - Granneman, James G.

AU - Mandrup, Susanne

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. We have used pharmacological inhibitors and a direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in cultured brown adipocytes. Here we show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, however, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on transcription and function of cultured brown adipocytes.

AB - β-Adrenergic signaling is a core regulator of brown adipocyte function stimulating both lipolysis and transcription of thermogenic genes, thereby expanding the capacity for oxidative metabolism. We have used pharmacological inhibitors and a direct activator of lipolysis to acutely modulate the activity of lipases, thereby enabling us to uncover lipolysis-dependent signaling pathways downstream of β-adrenergic signaling in cultured brown adipocytes. Here we show that induction of lipolysis leads to acute induction of several gene programs and is required for transcriptional regulation by β-adrenergic signals. Using machine-learning algorithms to infer causal transcription factors, we show that PPARs are key mediators of lipolysis-induced activation of genes involved in lipid metabolism and thermogenesis. Importantly, however, lipolysis also activates the unfolded protein response and regulates the core circadian transcriptional machinery independently of PPARs. Our results demonstrate that lipolysis generates important metabolic signals that exert profound pleiotropic effects on transcription and function of cultured brown adipocytes.

U2 - 10.1038/s41467-022-31525-8

DO - 10.1038/s41467-022-31525-8

M3 - Journal article

C2 - 35803907

AN - SCOPUS:85133673675

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3956

ER -

ID: 314439849