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

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 thermogenesisin brown adipose tissue(BAT) and that loss of TSK protects against diet-induced obesityand improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogeniccapacity, body weight regulation, and glucose homeostasis. Methods We measured the expression of thermogenicgenes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasiswere also assessed in the context of TSK loss and overexpression. Results The loss of TSK did not affect the thermogenicactivation 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 homeostasisin mice. Conclusions TSK is not a significant regulator of BAT thermogenesisand is unlikely to represent an effective target to prevent obesity and improve glucose homeostasis.