The mechanismus of leptin resistance in obesity and its improvement.

肥胖瘦素抵抗机制及其改善。

基本信息

批准号：
12672159
负责人：
UCHIDA Yoko
金额：
$ 1.09万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672159/
关键词：
leptin leptin resistance MSG obesity brown fat UCP gene expression thermogenesis 末梢産熱視床下部 Ob-Rb

项目摘要

To understand the mechanismus of leptin resistance in obesity, we examined the expression of ob gene receptors (OB-Rb, OB-Ra) and UCP family (UCP-1, UCP-2 and UCP-3) in the obese mice induced by monosodium-L-glutamate (MSG). We also assessed the effect of thermogenic adrenergic β3 agonist, BRL37344, on the gene expressions. Female ICR mice were subcutaneously injected with MSG (2 mg/g) every other day during the first 9 days of birth. At the age of 13-week-old, some mice received BRL37344 (0.1 mg/kg) for 2 weeks. Abundance for mRNA for ob gene receptors in hypothalamus and UCP family in adipose tissue (brown:BAT and white:WAT) and skeletal muscle was determined by RT-PCR. OB-Rb (long form) which is fanctionally active, predominates in the hypothalamus, but is also present at low levels in adipose tissue (BAT, WAT) and skeletal muscle. The expression of OB-Rb in hypothalamus was markedly reduced in MSG obese mice which may have leptin resistance. The expression of OB-Ra (short form), considered to lack signaling was observed both in hypothalamus and in peripheral tissues (BAT, WAT and skeletal muscle). However, the expression of OB-Ra in hypothalamus was not altered by MSG obesity. The expression of UCP-1 mRNA in BAT was increased in BRL37344-treated MSG mice, showing remain the response to adrenergic β3 agonist. The expression of UCP-2, which distributes in many tissues including BAT, WAT and skeletal muscle, was not affected by BRL37344 treatment. The expression of UCP-3, which is most abundant in skeletal muscle, increased in skeletal muscle and BAT, and was newly induced in WAT. Thus, it is suggested that leptin resistance in obese mice induced by MSG might be associated with down-regulation of hypothalamic ob gene receptor, especially OB -Rb.

为了了解观测中瘦素耐药性的机制，我们检查了由单磷酸L-glutamate（MSG）诱导的肥胖小鼠中OB基因受体（OB-RB，OB-RA）和UCP家族（UCP-1，UCP-2和UCP-3）的表达。我们还评估了热肾上腺素β3激动剂BRL37344对基因表达的影响。在出生后的前9天，每隔一天，每隔一天将雌性ICR小鼠皮下注射味精（2 mg/g）。在13周大的时候，一些小鼠接受了BRL37344（0.1 mg/kg）2周。 RT-PCR确定了脂肪组织下丘脑和UCP家族中OB基因受体（棕色：蝙蝠和白色：WAT）和骨骼肌中OB基因受体的丰度。 OB-RB（长形式）非常活跃，在下丘脑中占主导，但在脂肪组织（BAT，WAT）和骨骼肌中也存在低水平。在可能具有瘦素抗性的味精小鼠中，下丘脑中OB-RB的表达显着降低。在下丘脑和外周组织（蝙蝠，肠，WAT和骨骼肌）中观察到OB-RA（短形式）的表达，被认为缺乏信号传导。然而，下丘脑中OB-RA的表达并未因味精肥胖而改变。在BRL37344处理的MSG小鼠中，UCP-1 mRNA在BAT中的表达增加，表现出对肾上腺素能β3激动剂的反应。 UCP-2在包括BAT，WAT和骨骼肌在内的许多组织中分布的UCP-2的表达不受BRL37344治疗的影响。 UCP-3在骨骼肌中最丰富的UCP-3的表达增加了骨骼肌和蝙蝠，并在WAT中新诱导。这就是建议，由MSG诱导的肥胖小鼠中的瘦素耐药性可能与下丘脑OB基因受体的下调有关，尤其是OB -RB。