Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis

Rohollah Babaei, Maximilian Schuster, Irina Meln, Sarah Lerch, Rayane A. Ghandour, Didier F. Pisani, Irem Bayindir-Buchhalter, Julia Marx, Shuang Wu, Gabriele Schoiswohl, Adrian T. Billeter, Damir Krunic, Jan Mauer, Yun Hee Lee, James G. Granneman, Lars Fischer, Beat P. Müller-Stich, Ez Zoubir Amri, Erin E. Kershaw, Mathias HeikenwälderStephan Herzig, Alexandros Vegiopoulos

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGFβ signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.

Original languageEnglish
Article numbereaai7838
JournalScience Signaling
Volume11
Issue number527
DOIs
Publication statusPublished - 2018 Apr 24

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Adipogenesis
Adipocytes
Adipose Tissue
Tissue
Inflammation
White Adipose Tissue
Adrenergic Receptors
Chemical activation
Lipolysis
Stromal Cells
Interleukin-6
Transcription Factors
Phosphotransferases
Cytokines
Fats
Beige Adipocytes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Babaei, R., Schuster, M., Meln, I., Lerch, S., Ghandour, R. A., Pisani, D. F., ... Vegiopoulos, A. (2018). Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis. Science Signaling, 11(527), [eaai7838]. https://doi.org/10.1126/scisignal.aai7838
Babaei, Rohollah ; Schuster, Maximilian ; Meln, Irina ; Lerch, Sarah ; Ghandour, Rayane A. ; Pisani, Didier F. ; Bayindir-Buchhalter, Irem ; Marx, Julia ; Wu, Shuang ; Schoiswohl, Gabriele ; Billeter, Adrian T. ; Krunic, Damir ; Mauer, Jan ; Lee, Yun Hee ; Granneman, James G. ; Fischer, Lars ; Müller-Stich, Beat P. ; Amri, Ez Zoubir ; Kershaw, Erin E. ; Heikenwälder, Mathias ; Herzig, Stephan ; Vegiopoulos, Alexandros. / Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis. In: Science Signaling. 2018 ; Vol. 11, No. 527.
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Babaei, R, Schuster, M, Meln, I, Lerch, S, Ghandour, RA, Pisani, DF, Bayindir-Buchhalter, I, Marx, J, Wu, S, Schoiswohl, G, Billeter, AT, Krunic, D, Mauer, J, Lee, YH, Granneman, JG, Fischer, L, Müller-Stich, BP, Amri, EZ, Kershaw, EE, Heikenwälder, M, Herzig, S & Vegiopoulos, A 2018, 'Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis', Science Signaling, vol. 11, no. 527, eaai7838. https://doi.org/10.1126/scisignal.aai7838

Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis. / Babaei, Rohollah; Schuster, Maximilian; Meln, Irina; Lerch, Sarah; Ghandour, Rayane A.; Pisani, Didier F.; Bayindir-Buchhalter, Irem; Marx, Julia; Wu, Shuang; Schoiswohl, Gabriele; Billeter, Adrian T.; Krunic, Damir; Mauer, Jan; Lee, Yun Hee; Granneman, James G.; Fischer, Lars; Müller-Stich, Beat P.; Amri, Ez Zoubir; Kershaw, Erin E.; Heikenwälder, Mathias; Herzig, Stephan; Vegiopoulos, Alexandros.

In: Science Signaling, Vol. 11, No. 527, eaai7838, 24.04.2018.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Babaei, Rohollah

AU - Schuster, Maximilian

AU - Meln, Irina

AU - Lerch, Sarah

AU - Ghandour, Rayane A.

AU - Pisani, Didier F.

AU - Bayindir-Buchhalter, Irem

AU - Marx, Julia

AU - Wu, Shuang

AU - Schoiswohl, Gabriele

AU - Billeter, Adrian T.

AU - Krunic, Damir

AU - Mauer, Jan

AU - Lee, Yun Hee

AU - Granneman, James G.

AU - Fischer, Lars

AU - Müller-Stich, Beat P.

AU - Amri, Ez Zoubir

AU - Kershaw, Erin E.

AU - Heikenwälder, Mathias

AU - Herzig, Stephan

AU - Vegiopoulos, Alexandros

PY - 2018/4/24

Y1 - 2018/4/24

N2 - The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGFβ signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.

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Babaei R, Schuster M, Meln I, Lerch S, Ghandour RA, Pisani DF et al. Jak-TGFβ cross-talk links transient adipose tissue inflammation to beige adipogenesis. Science Signaling. 2018 Apr 24;11(527). eaai7838. https://doi.org/10.1126/scisignal.aai7838