Journal article
Adipose TBX1 regulates β-adrenergic sensitivity in subcutaneous adipose tissue and thermogenic capacity in vivo
Molecular metabolism (Germany), Vol.36, pp.100965-100965
06/2020
DOI: 10.1016/j.molmet.2020.02.008
PMID: 32240964
Abstract
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.
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.
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.
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.
•Transgenic overexpression of TBX1 specifically in adipose tissue is not sufficient to induce beiging of adipose tissues.•Expression of TBX1 in adipose is necessary for the defense of body temperature during cold exposure.•Adipose expression of TBX1 is necessary for maintaining insulin and β-adrenergic sensitivity in vivo.•TBX1 functions in adipose derived stem cells to regulate adipogenesis in a divergent manner in mouse versus man.
Details
- Title: Subtitle
- Adipose TBX1 regulates β-adrenergic sensitivity in subcutaneous adipose tissue and thermogenic capacity in vivo
- Creators
- Kathleen R Markan - Department of Neuroscience and Pharmacology, Iowa City, IA, 52242, USALauren K Boland - Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, 52242, USAAbdul Qaadir King-McAlpin - Department of Neuroscience and Pharmacology, Iowa City, IA, 52242, USAKristin E Claflin - Department of Neuroscience and Pharmacology, Iowa City, IA, 52242, USAMichael P Leaman - Department of Neuroscience and Pharmacology, Iowa City, IA, 52242, USAMorgan K Kemerling - Department of Neuroscience and Pharmacology, Iowa City, IA, 52242, USAMadison M Stonewall - Department of Neuroscience and Pharmacology, Iowa City, IA, 52242, USABrad A Amendt - Department of Anatomy and Cell Biology and the Craniofacial Anomalies Research Center, Iowa City, IA, 52242, USAJames A Ankrum - Fraternal Order of Eagles Diabetes Research Center, Iowa City, IA, 52242, USAMatthew J Potthoff - Department of Neuroscience and Pharmacology, Iowa City, IA, 52242, USA
- Resource Type
- Journal article
- Publication Details
- Molecular metabolism (Germany), Vol.36, pp.100965-100965
- DOI
- 10.1016/j.molmet.2020.02.008
- PMID
- 32240964
- NLM abbreviation
- Mol Metab
- ISSN
- 2212-8778
- eISSN
- 2212-8778
- Publisher
- Elsevier GmbH
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: K01DK111758, R01DK106104, F32 DK117510; DOI: 10.13039/100000054, name: National Cancer Institute, NIH, award: P30CA086862
- Language
- English
- Date published
- 06/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Neuroscience and Pharmacology; Dental Research
- Record Identifier
- 9984001085302771
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