Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers

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

Standard

Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers. / Loft, Anne; Forss, Isabel; Siersbæk, Majken Storm; Schmidt, Søren Fisker; Larsen, Ann-Sofie Bøgh; Madsen, Jesper Grud Skat; Pisani, Didier F; Nielsen, Ronni; Aagaard, Mads Malik; Mathison, Angela; Neville, Matt J; Urrutia, Raul; Karpe, Fredrik; Amri, Ez-Zoubir; Mandrup, Susanne.

In: Genes & Development, Vol. 29, 2015, p. 7-22.

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

Harvard

Loft, A, Forss, I, Siersbæk, MS, Schmidt, SF, Larsen, A-SB, Madsen, JGS, Pisani, DF, Nielsen, R, Aagaard, MM, Mathison, A, Neville, MJ, Urrutia, R, Karpe, F, Amri, E-Z & Mandrup, S 2015, 'Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers', Genes & Development, vol. 29, pp. 7-22. https://doi.org/10.1101/gad.250829.114

APA

Loft, A., Forss, I., Siersbæk, M. S., Schmidt, S. F., Larsen, A-S. B., Madsen, J. G. S., Pisani, D. F., Nielsen, R., Aagaard, M. M., Mathison, A., Neville, M. J., Urrutia, R., Karpe, F., Amri, E-Z., & Mandrup, S. (2015). Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers. Genes & Development, 29, 7-22. https://doi.org/10.1101/gad.250829.114

Vancouver

Loft A, Forss I, Siersbæk MS, Schmidt SF, Larsen A-SB, Madsen JGS et al. Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers. Genes & Development. 2015;29:7-22. https://doi.org/10.1101/gad.250829.114

Author

Loft, Anne ; Forss, Isabel ; Siersbæk, Majken Storm ; Schmidt, Søren Fisker ; Larsen, Ann-Sofie Bøgh ; Madsen, Jesper Grud Skat ; Pisani, Didier F ; Nielsen, Ronni ; Aagaard, Mads Malik ; Mathison, Angela ; Neville, Matt J ; Urrutia, Raul ; Karpe, Fredrik ; Amri, Ez-Zoubir ; Mandrup, Susanne. / Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers. In: Genes & Development. 2015 ; Vol. 29. pp. 7-22.

Bibtex

@article{66f2adf2ecd04a37998455808caa82f5,
title = "Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers",
abstract = "Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced browning of human adipocytes activates a comprehensive gene program that leads to increased mitochondrial oxidative capacity. Once induced, this gene program and oxidative capacity are maintained independently of rosiglitazone, suggesting that additional browning factors are activated. Browning triggers reprogramming of PPARγ binding, leading to the formation of PPARγ {"}superenhancers{"} that are selective for brown-in-white (brite) adipocytes. These are highly associated with key brite-selective genes. Based on such an association, we identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning, including the increase in mitochondrial oxidative capacity. KLF11 is directly induced by PPARγ and appears to cooperate with PPARγ in a feed-forward manner to activate and maintain the brite-selective gene program.",
keywords = "Adipocytes, Adipocytes, Brown, Cell Cycle Proteins, Cellular Reprogramming, Chromatin, Gene Expression Regulation, Humans, Hypoglycemic Agents, Mitochondria, Oxidation-Reduction, PPAR gamma, Protein Binding, Repressor Proteins, Thiazolidinediones, Transcriptional Activation",
author = "Anne Loft and Isabel Forss and Siersb{\ae}k, {Majken Storm} and Schmidt, {S{\o}ren Fisker} and Larsen, {Ann-Sofie B{\o}gh} and Madsen, {Jesper Grud Skat} and Pisani, {Didier F} and Ronni Nielsen and Aagaard, {Mads Malik} and Angela Mathison and Neville, {Matt J} and Raul Urrutia and Fredrik Karpe and Ez-Zoubir Amri and Susanne Mandrup",
note = "{\textcopyright} 2015 Loft et al.; Published by Cold Spring Harbor Laboratory Press.",
year = "2015",
doi = "10.1101/gad.250829.114",
language = "English",
volume = "29",
pages = "7--22",
journal = "Genes & Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",

}

RIS

TY - JOUR

T1 - Browning of human adipocytes requires KLF11 and reprogramming of PPARγ superenhancers

AU - Loft, Anne

AU - Forss, Isabel

AU - Siersbæk, Majken Storm

AU - Schmidt, Søren Fisker

AU - Larsen, Ann-Sofie Bøgh

AU - Madsen, Jesper Grud Skat

AU - Pisani, Didier F

AU - Nielsen, Ronni

AU - Aagaard, Mads Malik

AU - Mathison, Angela

AU - Neville, Matt J

AU - Urrutia, Raul

AU - Karpe, Fredrik

AU - Amri, Ez-Zoubir

AU - Mandrup, Susanne

N1 - © 2015 Loft et al.; Published by Cold Spring Harbor Laboratory Press.

PY - 2015

Y1 - 2015

N2 - Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced browning of human adipocytes activates a comprehensive gene program that leads to increased mitochondrial oxidative capacity. Once induced, this gene program and oxidative capacity are maintained independently of rosiglitazone, suggesting that additional browning factors are activated. Browning triggers reprogramming of PPARγ binding, leading to the formation of PPARγ "superenhancers" that are selective for brown-in-white (brite) adipocytes. These are highly associated with key brite-selective genes. Based on such an association, we identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning, including the increase in mitochondrial oxidative capacity. KLF11 is directly induced by PPARγ and appears to cooperate with PPARγ in a feed-forward manner to activate and maintain the brite-selective gene program.

AB - Long-term exposure to peroxisome proliferator-activated receptor γ (PPARγ) agonists such as rosiglitazone induces browning of rodent and human adipocytes; however, the transcriptional mechanisms governing this phenotypic switch in adipocytes are largely unknown. Here we show that rosiglitazone-induced browning of human adipocytes activates a comprehensive gene program that leads to increased mitochondrial oxidative capacity. Once induced, this gene program and oxidative capacity are maintained independently of rosiglitazone, suggesting that additional browning factors are activated. Browning triggers reprogramming of PPARγ binding, leading to the formation of PPARγ "superenhancers" that are selective for brown-in-white (brite) adipocytes. These are highly associated with key brite-selective genes. Based on such an association, we identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning, including the increase in mitochondrial oxidative capacity. KLF11 is directly induced by PPARγ and appears to cooperate with PPARγ in a feed-forward manner to activate and maintain the brite-selective gene program.

KW - Adipocytes

KW - Adipocytes, Brown

KW - Cell Cycle Proteins

KW - Cellular Reprogramming

KW - Chromatin

KW - Gene Expression Regulation

KW - Humans

KW - Hypoglycemic Agents

KW - Mitochondria

KW - Oxidation-Reduction

KW - PPAR gamma

KW - Protein Binding

KW - Repressor Proteins

KW - Thiazolidinediones

KW - Transcriptional Activation

U2 - 10.1101/gad.250829.114

DO - 10.1101/gad.250829.114

M3 - Journal article

C2 - 25504365

VL - 29

SP - 7

EP - 22

JO - Genes & Development

JF - Genes & Development

SN - 0890-9369

ER -

ID: 150711751