State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Białystok, Poland.
Cell Mol Life Sci. 2022 Jul 8;79(8):407. doi: 10.1007/s00018-022-04441-9.
Brown and beige adipose tissues dissipate chemical energy in the form of heat to maintain your body temperature in cold conditions. The impaired function of these tissues results in various metabolic diseases in humans and mice. By bioinformatical analyses, we identified a functional thermogenic regulator of adipose tissue, Androgen-dependent tissue factor pathway inhibitor [TFPI]-regulating protein (Adtrp), which was significantly overexpressed in and functionally activated the mature brown/beige adipocytes. Hereby, we knocked out Adtrp in mice which led to multiple abnormalities in thermogenesis, metabolism, and maturation of brown/beige adipocytes causing excess lipid accumulation in brown adipose tissue (BAT) and cold intolerance. The capability of thermogenesis in brown/beige adipose tissues could be recovered in Adtrp KO mice upon direct β3-adrenergic receptor (β3-AR) stimulation by CL316,243 treatment. Our mechanistic studies revealed that Adtrp by binding to S100 calcium-binding protein b (S100b) indirectly mediated the secretion of S100b, which in turn promoted the β3-AR mediated thermogenesis via sympathetic innervation. These results may provide a novel insight into Adtrp in metabolism via regulating the differentiation and thermogenesis of adipose tissues in mice.
棕色和米色脂肪组织以热量的形式消耗化学能量，以维持人体在寒冷环境中的体温。这些组织功能受损会导致人类和小鼠发生各种代谢疾病。通过生物信息学分析，我们鉴定出一种脂肪组织的功能性产热调节剂，雄激素依赖性组织因子途径抑制剂[TFPI]调节蛋白（Adtrp），它在成熟的棕色/米色脂肪细胞中显著过表达并具有功能性激活作用。因此，我们在小鼠中敲除了 Adtrp，导致产热、代谢和棕色/米色脂肪细胞成熟的多种异常，导致棕色脂肪组织（BAT）中脂质过度积累和不耐寒。在 Adtrp KO 小鼠中，通过 CL316,243 处理直接刺激β3-肾上腺素能受体（β3-AR），可以恢复棕色/米色脂肪组织的产热能力。我们的机制研究表明，Adtrp 通过与 S100 钙结合蛋白 b（S100b）结合，间接介导 S100b 的分泌，进而通过交感神经支配促进β3-AR 介导的产热。这些结果可能为 Adtrp 通过调节小鼠脂肪组织的分化和产热来影响代谢提供新的见解。
