Department of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.
Department of Biomedical Imaging and Image-Guided Therapy, High-Field MR Center, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.
Nat Commun. 2019 Jun 20;10(1):2717. doi: 10.1038/s41467-019-10684-1.
Hepatic steatosis develops when lipid influx and production exceed the liver's ability to utilize/export triglycerides. Obesity promotes steatosis and is characterized by leptin resistance. A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism. Since leptin mainly functions via CNS signaling, we here examine in rats whether leptin regulates hepatic lipid flux via the brain in a series of stereotaxic infusion experiments. We demonstrate that brain leptin protects from steatosis by promoting hepatic triglyceride export and decreasing de novo lipogenesis independently of caloric intake. Leptin's anti-steatotic effects are generated in the dorsal vagal complex, require hepatic vagal innervation, and are preserved in high-fat-diet-fed rats when the blood brain barrier is bypassed. Thus, CNS leptin protects from ectopic lipid accumulation via a brain-vagus-liver axis and may be a therapeutic strategy to ameliorate obesity-related steatosis.
当脂质流入和产生超过肝脏利用/输出甘油三酯的能力时，就会发生肝脂肪变性。肥胖会促进脂肪变性，并表现出瘦素抵抗。瘦素在肝脏脂质处理中的作用是通过观察到重组瘦素通过未知机制逆转脂肪营养不良患者的低瘦素血症性脂肪变性来突出显示的。由于瘦素主要通过中枢神经系统信号传导起作用，因此我们在这里通过一系列立体定向输注实验在大鼠中检查了瘦素是否通过大脑调节肝脏脂质通量。我们证明，脑内瘦素通过促进肝甘油三酯输出和减少从头合成脂质来防止脂肪变性，而与热量摄入无关。瘦素的抗脂肪变性作用是在迷走神经复合体中产生的，需要肝迷走神经支配，并且在血脑屏障被绕过时，在高脂肪饮食喂养的大鼠中得以保留。因此，中枢神经系统瘦素通过脑-迷走神经-肝轴来防止异位脂质积累，并且可能是改善肥胖相关脂肪变性的一种治疗策略。
