Leptin 蛋白, Human (His)

Leptin is a cytokine-like sugar secretory protein secreted by adipocytes that helps regulate energy balance by inhibiting food intake and increasing thermogenesis. Leptin can activate the JAK2-STAT3 and PI3K-AKT/mTOR pathways to regulate energy metabolism, prolong the QT interval via MAPK in the myocardium, and play a protective role in the gastric mucosa by inducing NO/CGRP release via the vagus nerve. Circulating CRP protein binds to leptin and blocks signal transduction, leading to obesity resistance. Leptin Protein, Human (His) is a recombinant human Leptin protein expressed by E. coli with N-6*His tag.

Leptin 是脂肪细胞分泌的一种激素，通过抑制摄食和增加产热来帮助调节能量平衡，属于细胞因子样蛋白家族。Leptin 的结构具有保守的四螺旋束构象，通过二硫键稳定三级结构，缺乏经典信号肽但通过非经典途径分泌。Leptin 的 C 端结构域介导受体结合，N 端区域促进寡聚化。Leptin 与下丘脑神经元及外周组织中的长型受体 OB-Rb 结合，激活 JAK2-STAT3 和 PI3K-AKT/mTOR 通路，抑制摄食并增强能量消耗。在心肌细胞中，Leptin 通过 OB-Rb 介导 MAPK 激活，降低心率并延长 QT 间期，该作用独立于 β-肾上腺素能信号^[1][2][3][4]。
在胃黏膜中，Leptin 通过迷走神经刺激感觉神经元释放 NO 和 CGRP，增强血流并保护组织免受缺血-再灌注损伤。循环 C 反应蛋白 (CRP) 与瘦素结合，阻断受体相互作用并减弱 STAT3 磷酸化，导致肥胖中的瘦素抵抗^[3][4]。Leptin 的上游调节因子包括脂肪细胞分泌的瘦素和肝脏合成的 CRP；下游靶点包括 STAT3、PI3K、eNOS 和 mTOR，发挥调控代谢、神经发生和血管功能的作用^[1][4]。
在代谢类疾病中，Leptin 抵抗与高瘦素血症及 CRP 介导的信号抑制相关，Leptin 补充可能抑制先天性脂肪营养不良和 2 型糖尿病^[4]。同时，Leptin 对心脏复极的直接作用 (QT 间期延长) 及其与 CRP 的相互作用可能参与肥胖相关的心律失常和动脉粥样硬化发生^[2]。Leptin 还通过迷走-感觉神经介导的 NO/CGRP 释放，增强胃黏膜血流并保护缺血损伤，可用于消化性溃疡疾病的研究^[3]。

Leptin 蛋白 (人源；0.5-16 nM；24 h) 剂量依赖性刺激人原代肝细胞的 C 反应蛋白 (CRP) 的分泌及 mRNA 表达，此效应可被 PI3K 抑制剂 LY294002 (HY-10108) 阻断^[1]。
Leptin 蛋白 (人源；10-1000 ng/mL；6-48 h) 可剂量依赖性促进人肺鳞癌细胞系 SQ-5 增殖，并激活 MAP 激酶活性，该效应可被 MEK-1 抑制剂 PD98059 (HY-12028) 阻断^[2]。
Leptin 蛋白 (人源；0.03 μg/mL，0.3 μg/mL；30 min-2 h) 可逆性延长分离的大鼠心室肌细胞的动作电位时程，在复极期诱导晚期平台相^[3]。

Leptin 蛋白 (人源；0.3 mg/kg/d；渗透泵皮下输注；每日 1 次；6 d) 在 ob/ob 小鼠中减少食物摄入、体重、血糖、血清胰岛素和肝甘油三酯，并激活下丘脑 STAT3 磷酸化，而与人 C-reactive 蛋白 (40 mg/d，CRP) 共输注则阻断这些效应^[1]。
Leptin 蛋白 (人源；0.6 mg/kg/d；渗透泵皮下输注；每日 1 次) 不会降低人 CRP 转基因小鼠的食物摄入、体重或附睾脂肪垫重量，而在野生型同窝小鼠中显著诱导降低^[1]。
Leptin 蛋白 (人源；0.1-30 μg/kg；静脉注射；单剂量；急性) 剂量依赖性降低大鼠的静息心率，而高剂量下 (150-300 μg/kg)，Leptin 蛋白可诱导双相效应 (先降后升) ，并增加 QT 间期和心室动作电位时程，部分效应通过独立于 β-肾上腺素能受体的瘦素受体介导^[3]。
Leptin 蛋白 (人源；10 μg/kg；腹腔注射；单剂量；急性) 减轻大鼠受缺血-再灌注诱导的胃损伤，增加胃血流

Fully biologically active determined by the dose dependent proliferation of MCF7 cells. The ED₅₀ for this effect is 14.64 ng/mL, corresponding to a specific activity is 6.83×10⁴ units/mg.

• 
  Fully biologically active determined by the dose dependent proliferation of MCF7 cells. The ED₅₀ for this effect is 14.64 ng/mL, corresponding to a specific activity is 6.83×10⁴ units/mg.

Human

E. coli

N-6*His

P41159 (V22-C167)

3952  [NCBI]

Full Length of Mature Protein

VPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGLDFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC

Approximately 17 kDa

• 
  Greater than 95% as determined by reducing SDS-PAGE

无菌粉末.

Lyophilized from a 0.22 μm filtered solution of 50 mM Tris-HCl, 300 mM NaCl, 200 mM arginine, pH 8.0.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Chen K, et al. Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med. 2006 Apr;12(4):425-32.  [Content Brief]

  [2]. Tsuchiya T, et al. Expression of leptin receptor in lung: leptin as a growth factor. Eur J Pharmacol. 1999 Jan 22;365(2-3):273-9.  [Content Brief]

  [3]. Lin YC, et al. Leptin decreases heart rate associated with increased ventricular repolarization via its receptor. Am J Physiol Heart Circ Physiol. 2015 Nov 15;309(10):H1731-9.  [Content Brief]

  [4]. Brzozowski T, et al. Brain-gut axis in gastroprotection by leptin and cholecystokinin against ischemia-reperfusion induced gastric lesions. J Physiol Pharmacol. 2001 Dec;52(4 Pt 1):583-602.  [Content Brief]