Proper regulation of β-adrenergic signal requires Btg2 gene for lipolysis and thermogenesis in response to starvation or cold acclimation in female mice

Mammals maintain constant body temperature in cold environment by activating thermogenesis via adrenergic/protein kinase A (PKA) signaling. B-cell translocation gene 2 (BTG2/Tis21), induced by PKA signaling, regulates glucose and lipid metabolism in liver, yet its role in lipolysis and in thermogenesis is not explored. Here, Btg2-knockout (KO) mice failed to maintain body temperature under starvation, or in cold acclimation. And norepinephrine-induced thermogenic response was turned off earlier in the KO mice. Gender specifically, gonadal white adipose tissues (gWAT) of female-KO were very active in lipolysis in fed state, however, the fat degradation was diminished upon fasting or cold acclimation. Also, insulin sensitivity was increased in female-KO, but not in male-KO mice, along with the low bone mineral density and small brown adipose tissues (BAT). In the mechanistic aspect, expressions of UCP1 and lipases (LPL, ATGL, HSL) in gWAT of female-KO mice were significantly reduced in response to adrenergic signals. Here, we present some data that Btg2 gene is essential for properly respond to β-adrenergic signals, and plays as a negative regulator of insulin signaling in female mice.