The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis

Mathilde Mouchiroud, Étienne Camiré, Manal Aldow, Alexandre Caron, Éric Jubinville, Laurie Turcotte, Inés Kaci, Marie Josée Beaulieu, Christian Roy, Sébastien M. Labbé, Thibault V. Varin, Yves Gélinas, Jennifer Lamothe, Jocelyn Trottier, Patricia L. Mitchell, Frédéric Guénard, William T. Festuccia, Philippe Joubert, Christopher F. Rose, Constantine J. KarvellasOlivier Barbier, Mathieu C. Morissette, André Marette, Mathieu Laplante

Research output: Contribution to journalArticle

Abstract

Objectives: Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis. Methods: We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression. Results: The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice. Conclusions: TSK is not a significant regulator of BAT thermogenesis and is unlikely to represent an effective target to prevent obesity and improve glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)184-191
Number of pages8
JournalMolecular Metabolism
Volume30
DOIs
StatePublished - Dec 2019

Keywords

  • Brown adipose tissue
  • Glucose homeostasis
  • Hepatokine
  • Obesity
  • Thermogenesis
  • Tsukushi

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Mouchiroud, M., Camiré, É., Aldow, M., Caron, A., Jubinville, É., Turcotte, L., Kaci, I., Beaulieu, M. J., Roy, C., Labbé, S. M., Varin, T. V., Gélinas, Y., Lamothe, J., Trottier, J., Mitchell, P. L., Guénard, F., Festuccia, W. T., Joubert, P., Rose, C. F., ... Laplante, M. (2019). The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis. Molecular Metabolism, 30, 184-191. https://doi.org/10.1016/j.molmet.2019.09.014