Abstract：
Upon fasting, adipocytes release their lipids that accumulate in the liver, thus promoting hepatic steatosis and ketone body production. However, the mechanisms underlying this process are not fully understood. In this study, we found that fasting caused a substantial decrease in the adipose levels of RUBCN/rubicon, a negative regulator of macroautophagy/autophagy, along with an increase in autophagy. Adipose-specific rubcn-knockout mice exhibited systemic fat loss that was not accelerated by fasting. Genetic inhibition of autophagy in adipocytes in fasted mice led to a reduction in fat loss, hepatic steatosis, and ketonemia. In terms of mechanism, autophagy decreased the levels of its substrates NCOA1/SRC-1 and NCOA2/TIF2, which are also coactivators of PPARG/PPARγ, leading to a fasting-induced reduction in the mRNA levels of adipogenic genes in adipocytes. Furthermore, RUBCN in adipocytes was degraded through the autophagy pathway, suggesting that autophagic degradation of RUBCN serves as a feedforward system for autophagy induction during fasting. Collectively, we propose that loss of adipose RUBCN promotes a metabolic response to fasting via increasing autophagic activity.
摘要：
在禁食时，脂肪细胞释放它们在肝脏中积累的脂质，从而促进肝脏脂肪变性和酮体的产生。然而,这一过程背后的机制还没有完全理解。在这项研究中,我们发现禁食导致RUBCN/rubicon的脂肪水平大幅下降，巨自噬/自噬的负调节因子，随着自噬的增加。脂肪特异性rubcn敲除小鼠表现出全身性脂肪损失，但禁食并未加速。对禁食小鼠脂肪细胞自噬的遗传抑制导致脂肪减少，肝脂肪变性,还有酮症.在机制方面,自噬降低其底物NCOA1/SRC-1和NCOA2/TIF2的水平，它们也是PPARG/PPARγ的共激活剂，导致空腹诱导的脂肪细胞中脂肪生成基因的mRNA水平降低。此外，脂肪细胞中的RUBCN通过自噬途径降解，这表明RUBCN的自噬降解是禁食期间自噬诱导的前馈系统。总的来说，我们认为脂肪RUBCN的减少通过增加自噬活性促进对禁食的代谢反应.
