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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.

为了解瘦素抵抗在肥胖中的作用机制，本研究检测了L-谷氨酸单钠（MSG）诱导的肥胖小鼠ob基因受体（OB-Rb、OB-Ra）和UCP家族（UCP-1、UCP-2和UCP-3）的表达。我们还评估了产热肾上腺素能β 3激动剂BRL 37344对基因表达的影响。雌性ICR小鼠在出生的前9天内每隔一天皮下注射MSG（2mg/g）。在13周龄时，一些小鼠接受BRL 37344（0.1 mg/kg）2周。用RT-PCR方法检测下丘脑ob基因受体和UCP家族在脂肪组织（棕色：BAT和白色：WAT）和骨骼肌中的mRNA表达。OB-Rb（长型）具有功能活性，主要存在于下丘脑中，但也以低水平存在于脂肪组织（BAT，WAT）和骨骼肌中。MSG肥胖小鼠下丘脑OB-Rb表达明显减少，可能存在瘦素抵抗。在下丘脑和外周组织（BAT、WAT和骨骼肌）中均观察到被认为缺乏信号传导的OB-Ra（短形式）的表达。而下丘脑OB-Ra的表达则不受MSG肥胖的影响。BRL 37344处理的MSG小鼠BAT中UCP-1 mRNA表达增加，显示对肾上腺素能β 3受体激动剂的反应。BRL 37344处理对UCP-2的表达没有影响，UCP-2分布在BAT、WAT和骨骼肌等多种组织中。在骨骼肌中最丰富的UCP-3的表达在骨骼肌和BAT中增加，并且在WAT中被新诱导。提示MSG诱导肥胖小鼠瘦素抵抗可能与下丘脑ob基因受体尤其是OB-Rb表达下调有关。