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林奈提取物可增加弓状核瘦素受体的 mRNA 表达,并有望成为一种抗肥胖药物。

Linn. Extract Increases the mRNA Expression of the Arcuate Nucleus Leptin Receptor and is Predicted as an Anti-obesity Agent.

机构信息

Departement of Medical Physiology, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia.

Master's Programme in Biomedical Science, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia.

出版信息

Curr Comput Aided Drug Des. 2024;20(6):811-821. doi: 10.2174/1573409920666230822115144.

Abstract

BACKGROUND

Leptin is predominant in regulating body weight by stimulating energy expenditure through its neuronal action in the brain. Moreover, it is projected to adipose tissue and induces adipocyte browning by activating the β3-adrenergic receptor (β3AR). However, the expression of leptin receptor (Lep-R) and β3AR in people with obesity is downregulated.

AIM

We hypothesized that Linn. extract (HSE) would increase hypothalamus arcuate nucleus (ARC) Lep-R and white adipose tissue (WAT) β3AR mRNA expression in DIO rats. This study also analyzed the potency of bioactive compounds as activators of Lep-R and β3AR by an experiment.

METHODS

Twenty-four male rats were divided into four groups: Control (standard food), DIO (high-fat diet), DIO-Hib200 (HFD+HSE 200 mg/kg BW), and DIO-Hib400 (HFD+HSE400 mg/kg BW). HSE was administered orally for five weeks, once a day.

RESULTS

HSE administration significantly (p <0,05) increased the ARC Lep-R expression. The Lee index significantly decreased to the normal range (≤ 310) with p <0,001 for DIO-Hib200 and p <0,01 for DIO-Hib400. Among 39 bioactive compounds, acid exhibited high free binding scores (-8,63) for Lep-R, and had high free binding scores (-9,39) for β3AR. These binding predictions could activate Lep-R and β3AR.

CONCLUSION

This study highlights that HSE could be a potential therapeutic target for obesity by increasing LepR mRNA and leptin sensitivity, enhancing energy expenditure, and reducing obesity.

摘要

背景

瘦素通过其在大脑中的神经元作用刺激能量消耗,从而在调节体重方面占主导地位。此外,它被投射到脂肪组织,并通过激活β3-肾上腺素能受体(β3AR)诱导脂肪细胞棕色化。然而,肥胖人群的瘦素受体(Lep-R)和β3AR 的表达下调。

目的

我们假设 Linn. 提取物(HSE)会增加 DIO 大鼠下丘脑弓状核(ARC)Lep-R 和白色脂肪组织(WAT)β3AR mRNA 的表达。本研究还通过实验分析了生物活性化合物作为 Lep-R 和 β3AR 激活剂的效力。

方法

将 24 只雄性大鼠分为四组:对照组(标准饮食)、DIO 组(高脂肪饮食)、DIO-Hib200 组(HFD+HSE 200mg/kg BW)和 DIO-Hib400 组(HFD+HSE400mg/kg BW)。HSE 每天口服一次,连续五周。

结果

HSE 给药显著(p<0.05)增加了 ARC Lep-R 的表达。Lee 指数显著降低至正常范围(≤310),DIO-Hib200 组 p<0.001,DIO-Hib400 组 p<0.01。在 39 种生物活性化合物中,酸对 Lep-R 表现出高的游离结合评分(-8.63),而对β3AR 具有高的游离结合评分(-9.39)。这些结合预测可以激活 Lep-R 和β3AR。

结论

本研究强调,HSE 可以通过增加 LepR mRNA 和瘦素敏感性、增强能量消耗和减少肥胖,成为肥胖的潜在治疗靶点。

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