OHBA Ken-ichi Tokyo Women's Medical University, School of Medicine, Research Associate, 医学部, 助手 (60256477)
TSUKAHARA Fujiko Tokyo Women's Medical University, School of Medicine, Research Associate, 医学部, 助手 (40119996)
MURAKI Takamura Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (50051446)
|Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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.