TY - JOUR
T1 - The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis
AU - Mouchiroud, Mathilde
AU - Camiré, Étienne
AU - Aldow, Manal
AU - Caron, Alexandre
AU - Jubinville, Éric
AU - Turcotte, Laurie
AU - Kaci, Inés
AU - Beaulieu, Marie Josée
AU - Roy, Christian
AU - Labbé, Sébastien M.
AU - Varin, Thibault V.
AU - Gélinas, Yves
AU - Lamothe, Jennifer
AU - Trottier, Jocelyn
AU - Mitchell, Patricia L.
AU - Guénard, Frédéric
AU - Festuccia, William T.
AU - Joubert, Philippe
AU - Rose, Christopher F.
AU - Karvellas, Constantine J.
AU - Barbier, Olivier
AU - Morissette, Mathieu C.
AU - Marette, André
AU - Laplante, Mathieu
N1 - Funding Information:
The authors are grateful to Yves Deshaies for advice. This work was supported by grants from the Canadian Institutes of Health Research (CIHR) ( 271671 , 374552 , and FDN143247 ), Les Fonds de recherche du Québec–Santé (FRQS) ( 24726 ), Le Réseau de recherche en santé cardiométabolique, diabète et obésité (CMDO) , Le Réseau de bio-imagerie du Québec (RBIQ) , Diabète Québec , La Fondation de l’Institut universitaire de cardiologie et de pneumologie de Québec–Université Laval (IUCPQ-UL) , and Merck Sharpe and Dohme Corp / Faculté de Médecine de l’Université Laval to M.L. Alexandre Caron is a CIHR Banting postdoctoral fellow.
Publisher Copyright:
© 2019 The Author(s)
PY - 2019/12
Y1 - 2019/12
N2 - 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.
AB - 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.
KW - Brown adipose tissue
KW - Glucose homeostasis
KW - Hepatokine
KW - Obesity
KW - Thermogenesis
KW - Tsukushi
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U2 - 10.1016/j.molmet.2019.09.014
DO - 10.1016/j.molmet.2019.09.014
M3 - Article
C2 - 31767170
AN - SCOPUS:85074321789
SN - 2212-8778
VL - 30
SP - 184
EP - 191
JO - Molecular Metabolism
JF - Molecular Metabolism
ER -