Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, France.
Laboratoire de Spectrométrie de Masse Bio-Organique, 25 rue Becquerel, F-67087 Strasbourg, France.
Biol Chem. 2020 Feb 25;401(3):389-405. doi: 10.1515/hsz-2019-0184.
Various pathophysiological situations of negative energy balance involve the intense depletion of the body's energy reserves. White adipose tissue is a central place to store energy and a major endocrine organ. As a model of choice to better understand how the white adipose tissue dynamically responds to changes in substrate availability, we used the prolonged fasting paradigm, which is characterized by successive periods of stimulated (phase 2) and then reduced (phase 3) lipid mobilization/utilization. Using omics analyses, we report a regulatory transcriptional program in rat epididymal (EPI) adipose tissue favoring lipolysis during phase 2 and repressing it during phase 3. Changes in gene expression levels of lipases, lipid droplet-associated factors, and the proteins involved in cAMP-dependent and cAMP-independent regulation of lipolysis are highlighted. The mRNA and circulating levels of adipose-secreted factors were consistent with the repression of insulin signaling during prolonged fasting. Other molecular responses are discussed, including the regulation of leptin and adiponectin levels, the specific changes reflecting an increased fibrinolysis and a possible protein catabolism-related energy saving mechanism in late fasting. Finally, some differences between internal and subcutaneous (SC) adipose tissues are also reported. These data provide a comprehensive molecular basis of adipose tissue responses when facing a major energetic challenge.
各种负能平衡的病理生理情况涉及到机体能量储备的大量消耗。白色脂肪组织是储存能量的中心场所，也是主要的内分泌器官。作为更好地理解白色脂肪组织如何动态响应底物可用性变化的模型选择，我们使用了延长的禁食范式，其特征是连续的刺激期（第 2 期）和随后的减少期（第 3 期）脂质动员/利用。通过组学分析，我们报告了大鼠附睾（EPI）脂肪组织中的一个调节转录程序，该程序在第 2 期有利于脂肪分解，在第 3 期抑制脂肪分解。强调了脂肪酶、脂滴相关因子的基因表达水平的变化，以及涉及 cAMP 依赖性和 cAMP 非依赖性脂肪分解调节的蛋白质。脂肪分泌因子的 mRNA 和循环水平与延长禁食期间胰岛素信号的抑制一致。还讨论了其他分子反应，包括瘦素和脂联素水平的调节，反映在晚期禁食时纤溶增加和可能与蛋白质分解代谢相关的能量节约机制的特定变化。最后，还报告了内部和皮下（SC）脂肪组织之间的一些差异。这些数据提供了在面临重大能量挑战时脂肪组织反应的综合分子基础。
