Little is known about the influence of central nesfatin‐1 on lipid metabolism under diabetic conditions. The main objective of this study was to characterize the mechanisms by which central nesfatin‐1 regulates lipid metabolism in streptozotocin (STZ)‐induced type 2 diabetes mellitus (T2DM) and whether the sympathetic nervous system is involved. Male Kunming mice were fed high‐fat diets (HFDs) and were treated twice with low‐dose STZ (100 mg/kg, intraperitoneal [IP]) to generate the T2DM model. Pharmacological adrenergic blockage (phentolamine 10 mg/kg, propranolol 0.017 mmol) and surgical denervation of sympathetic nervous system of the hindlimb and inguinal fat were used to block nerve conduction to determine whether the effect of central nesfatin‐1 required the hypothalamic‐sympathetic nervous system axis. Plasma free fatty acid (FFA) and insulin levels were measured. AMP‐activated protein kinase (AMPK) levels in skeletal muscle and hormone‐sensitive lipase and adipose triglycerides lipase (HSL/ATGL) levels in white adipose tissue (WAT) were measured using western blot. mRNA expression of AMPK was measured. We found that there were significantly fewer NUCB2/nesfatin‐1 immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) in T2DM mice. Central nesfatin‐1 administration decreased levels of plasma FFA significantly and activated AMPK to enhance fatty‐acid oxidation in skeletal muscle in T2DM mice. In addition, HSL and ATGL were significantly activated during triglyceride mobilization in WAT triggered by central nesfatin‐1 administration. Adrenergic blockade and morphological denervation of the sciatic and femoral nerves reduced these changes. Taken together, these data suggest that central nesfatin‐1 regulates peripheral lipid metabolism in type 2 diabetes via the sympathetic nervous system.

中文翻译：

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中枢nesfatin-1通过交感神经系统激活脂肪组织中的脂质动员和肌肉中的脂肪酸氧化。

关于中枢nesfatin-1对糖尿病条件下脂质代谢的影响知之甚少。这项研究的主要目的是表征中枢nesfatin-1调节链脲佐菌素（STZ）诱导的2型糖尿病（T2DM）的脂质代谢的机制，以及是否涉及交感神经系统。给昆明雄性小鼠喂食高脂饮食（HFD），并用低剂量STZ（100 mg / kg，腹膜内[IP]）治疗两次，以建立T2DM模型。使用药理学上的肾上腺素能阻滞剂（酚妥拉明10 mg / kg，普萘洛尔0.017 mmol）以及后肢交感神经系统和腹股沟脂肪的手术神经支配来阻断神经传导，以确定中枢nesfatin-1的作用是否需要下丘脑-交感神经系统。轴。测量血浆游离脂肪酸（FFA）和胰岛素水平。使用蛋白质印迹法测量骨骼肌中AMP活化的蛋白激酶（AMPK）水平以及白色脂肪组织（WAT）中的激素敏感性脂肪酶和脂肪甘油三酸酯脂肪酶（HSL / ATGL）水平。测量AMPK的mRNA表达。我们发现T2DM小鼠的室旁核（PVN）和视上核（SON）的NUCB2 / nesfatin-1免疫反应性神经元明显减少。中央nesfatin-1给药可显着降低血浆FFA水平，并激活AMPK以增强T2DM小鼠骨骼肌中的脂肪酸氧化。此外，在由中央nesfatin-1给药触发的WAT中甘油三酸酯动员期间，HSL和ATGL被显着激活。坐骨神经和股神经的肾上腺素能阻滞和形态失神经减少了这些改变。综上所述，这些数据表明中枢nesfatin-1通过交感神经系统调节2型糖尿病的外周脂质代谢。