The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis
Open accessAbstract
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.
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Results with TSK knockout mice and TSK administration were not reproduced in a subsequent study.
“However, these results with TSK knockout mice and TSK administration were not reproduced in a subsequent study [272].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [272]
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Hepatokines and metabolism: Deciphering communication from the liver
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- Authors
- 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., Karvellas, C. J., Barbier, O., Morissette, M. C., Marette, A., & Laplante, M.
- Affiliations
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- The University of Texas Southwestern Medical Center (US)
- Centre hospitalier universitaire de Québec (CA)
- Université Laval (CA)
- Universidade de São Paulo (BR)
- Centre Hospitalier de l’Université de Montréal (CA)
- University of Alberta (CA)
- Corresponding author
- Laplante, Mathieu
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 30
- Pages
- 184-191
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC6889588
- OpenAlex
- W2977716298
- Cited by
- 24
- References
- 24
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 3
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Papyrus : Institutional Repository (Université de Montréal) (submittedVersion, cc-by)
- Funders
- Fonds de Recherche du Québec - Santé (24726)
- Canadian Institutes of Health Research (374552, 271671, FDN143247)
- Merck Sharp and Dohme
- Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval
- Faculté de Médecine, Université Laval
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- Tsukushi, hepatokines, brown adipose tissue, thermogenesis, diet-induced obesity, glucose homeostasis, body weight regulation, sympathetic innervation, cold exposure, obesity prevention
- MeSH terms
- Animals, Body Weight, Adipose Tissue, Brown, Female, Glucose, Homeostasis, Male, Mice, Inbred C57BL, Obesity, Proteoglycans, Weight Gain, Mice, Knockout, Thermogenesis, Intercellular Signaling Peptides and Proteins, Mice
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