TY - JOUR
T1 - Adipose TBX1 regulates β-adrenergic sensitivity in subcutaneous adipose tissue and thermogenic capacity in vivo
AU - Markan, Kathleen R.
AU - Boland, Lauren K.
AU - King-McAlpin, Abdul Qaadir
AU - Claflin, Kristin E.
AU - Leaman, Michael P.
AU - Kemerling, Morgan K.
AU - Stonewall, Madison M.
AU - Amendt, Brad A.
AU - Ankrum, James A.
AU - Potthoff, Matthew J.
N1 - Funding Information:
The authors thank Drs. Adam Rauckhorst and Brett Wagner (University of Iowa) for technical assistance and insightful discussions. This work was supported by the National Institutes of Health (NIH) K01DK111758 (K R M), R01DK106104 (M.J.P.), F32 DK117510 (K.E.C.), and in part by the National Cancer Institute, NIH ) P30CA086862 (University of Iowa ESR Core). K.R.M. conceived of, designed and conducted experiments. L.K.B., A.Q.K.M., K.E.C, M.P.L., M.K.K. and M.M.S. conducted experiments and performed data analysis. K.R.M. and M.J.P. wrote the manuscript. K.R.M is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Publisher Copyright:
© 2020 The Authors
PY - 2020/6
Y1 - 2020/6
N2 - Objective: T-box 1 (TBX1) has been identified as a genetic marker of beige adipose tissue. TBX1 is a mesodermal development transcription factor essential for tissue patterning and cell fate determination. However, whether it plays a role in the process of adipose beiging or how it functions in adipose tissue has not been reported. Here, we examined the function of TBX1 in adipose tissue as well as adipose-derived stem cells from mice and humans. Methods: Adipose-specific TBX1 transgenic (TBX1 AdipoTG) and adipose-specific TBX1 knockout (TBX1 AdipoKO) mice were generated to explore the function of TBX1 in the process of adipose beiging, metabolism and energy homeostasis in vivo. In vitro, we utilized a siRNA mediated approach to determine the function of TBX1 during adipogenesis in mouse and human stem cells. Results: Adipose-specific overexpression of TBX1 was not sufficient to fully induce beiging and prevent diet-induced obesity. However, adipose TBX1 expression was necessary to defend body temperature during cold through regulation of UCP1 and for maintaining β3-adrenergic sensitivity and glucose homeostasis in vivo. Loss of adipose TBX1 expression enhanced basal lipolysis and reduced the size of subcutaneous iWAT adipocytes. Reduction of TBX1 expression via siRNA significantly impaired adipogenesis of mouse stromal vascular cells but significantly enhanced adipogenesis in human adipose derived stem cells. Conclusions: Adipose expression of TBX1 is necessary, but not sufficient, to defend body temperature during cold via proper UCP1 expression. Adipose TBX1 expression was also required for proper insulin signaling in subcutaneous adipose as well as for maintaining β-adrenergic sensitivity, but overexpression of TBX1 was not sufficient to induce adipocyte beiging or to prevent diet-induced obesity. TBX1 expression is enriched in adipose stem cells in which it has contrasting effects on adipogenesis in mouse versus human cells. Collectively, these data demonstrate the importance of adipose TBX1 in the regulation of beige adipocyte function, energy homeostasis, and adipocyte development.
AB - Objective: T-box 1 (TBX1) has been identified as a genetic marker of beige adipose tissue. TBX1 is a mesodermal development transcription factor essential for tissue patterning and cell fate determination. However, whether it plays a role in the process of adipose beiging or how it functions in adipose tissue has not been reported. Here, we examined the function of TBX1 in adipose tissue as well as adipose-derived stem cells from mice and humans. Methods: Adipose-specific TBX1 transgenic (TBX1 AdipoTG) and adipose-specific TBX1 knockout (TBX1 AdipoKO) mice were generated to explore the function of TBX1 in the process of adipose beiging, metabolism and energy homeostasis in vivo. In vitro, we utilized a siRNA mediated approach to determine the function of TBX1 during adipogenesis in mouse and human stem cells. Results: Adipose-specific overexpression of TBX1 was not sufficient to fully induce beiging and prevent diet-induced obesity. However, adipose TBX1 expression was necessary to defend body temperature during cold through regulation of UCP1 and for maintaining β3-adrenergic sensitivity and glucose homeostasis in vivo. Loss of adipose TBX1 expression enhanced basal lipolysis and reduced the size of subcutaneous iWAT adipocytes. Reduction of TBX1 expression via siRNA significantly impaired adipogenesis of mouse stromal vascular cells but significantly enhanced adipogenesis in human adipose derived stem cells. Conclusions: Adipose expression of TBX1 is necessary, but not sufficient, to defend body temperature during cold via proper UCP1 expression. Adipose TBX1 expression was also required for proper insulin signaling in subcutaneous adipose as well as for maintaining β-adrenergic sensitivity, but overexpression of TBX1 was not sufficient to induce adipocyte beiging or to prevent diet-induced obesity. TBX1 expression is enriched in adipose stem cells in which it has contrasting effects on adipogenesis in mouse versus human cells. Collectively, these data demonstrate the importance of adipose TBX1 in the regulation of beige adipocyte function, energy homeostasis, and adipocyte development.
KW - Adipose
KW - Beige
KW - Brite
KW - Subcutaneous
KW - Tbx1
KW - Thermogenesis
UR - http://www.scopus.com/inward/record.url?scp=85082465727&partnerID=8YFLogxK
U2 - 10.1016/j.molmet.2020.02.008
DO - 10.1016/j.molmet.2020.02.008
M3 - Article
C2 - 32240964
AN - SCOPUS:85082465727
SN - 2212-8778
VL - 36
JO - Molecular Metabolism
JF - Molecular Metabolism
M1 - 100965
ER -