Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA; Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan.
Case Cardiovascular Research Institute, Department of Medicine, Case Western Reserve University School of Medicine, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Cell Rep. 2017 Dec 12;21(11):3129-3140. doi: 10.1016/j.celrep.2017.11.032.
Adipose tissue stores energy in the form of triglycerides. The ability to regulate triglyceride synthesis and breakdown based on nutrient status (e.g., fed versus fasted) is critical for physiological homeostasis and dysregulation of this process can contribute to metabolic disease. Whereas much is known about hormonal control of this cycle, transcriptional regulation is not well understood. Here, we show that the transcription factor Kruppel-like factor 15 (KLF15) is critical for the control of adipocyte lipid turnover. Mice lacking Klf15 in adipose tissue (AK15KO) display decreased adiposity and are protected from diet-induced obesity. Mechanistic studies suggest that adipose KLF15 regulates key genes of triglyceride synthesis and inhibits lipolytic action, thereby promoting lipid storage in an insulin-dependent manner. Finally, AK15KO mice demonstrate accelerated lipolysis and altered systemic energetics (e.g., locomotion, ketogenesis) during fasting conditions. Our study identifies adipose KLF15 as an essential regulator of adipocyte lipid metabolism and systemic energy balance.
脂肪组织以甘油三酯的形式储存能量。根据营养状况（例如，进食状态与禁食状态）调节甘油三酯合成和分解的能力对于生理稳态至关重要，而这种过程的失调可能导致代谢疾病。虽然人们对激素对该循环的控制了解很多，但转录调控却知之甚少。在这里，我们表明转录因子 Kruppel 样因子 15（KLF15）对于控制脂肪细胞脂质周转至关重要。脂肪组织中缺乏 Klf15 的小鼠（AK15KO）表现出脂肪减少，并能防止饮食引起的肥胖。机制研究表明，脂肪组织中的 KLF15 调节甘油三酯合成的关键基因，并抑制脂肪分解作用，从而以胰岛素依赖的方式促进脂质储存。最后，AK15KO 小鼠在禁食状态下表现出脂肪分解加速和全身能量代谢的改变（例如，运动，酮体生成）。我们的研究确定脂肪组织 KLF15 是脂肪细胞脂质代谢和全身能量平衡的重要调节剂。
