Calorie restriction-mediated restoration of hypothalamic signal transducer and activator of transcription 3 (STAT3) phosphorylation is not effective for lowering the body weight set point in IRS-2 knockout obese mice
Calorie restriction-mediated restoration of hypothalamic signal transducer and activator of transcription 3 (STAT3) phosphorylation is not effective for lowering the body weight set point in IRS-2 knockout obese mice
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热量限制介导的下丘脑信号转导子和转录激活子 3 (STAT3) 磷酸化恢复对于降低 IRS-2 敲除肥胖小鼠的体重设定点无效
DOI：
10.1007/s13340-015-0205-3
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发表时间：
2015
影响因子：
2.2
通讯作者：
Kadowaki T and Tobe K.
中科院分区：
文献类型：
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作者：
Senda S;Inoue A;Mahmood A;Suzuki R;Kamei N;Kubota N;Watanabe T;Aoyama M;Nawaz A;Ohkuma Y;Tsuneyama K;Koshimizu Y;Usui I;Saeki K;Kadowaki T and Tobe K.
目的/假设降低体重设定点是维持体重减轻的前提条件。在这种情况下，肥胖症是众所周知的密切相关的瘦素抵抗，它仍然有待澄清是否从瘦素抵抗的恢复可能会降低体重设定点，让持续的体重loss.MethodsObese IRS-2敲除（IRS-2-/-）小鼠进行热量限制（CR）或β3-肾上腺素能受体（AR）激动剂治疗。瘦素的生理效应，下丘脑瘦素信号，和改变的体重setpoint.ResultsIn的CR小鼠，从获得性瘦素抵抗的恢复观察，如所示的恢复瘦素对食物摄入量和体重增加的抑制作用，以及信号转导和转录激活因子3（STAT 3）磷酸化的恢复。然而，在停止CR后，体重迅速反弹至原始体重，表明CR未能克服IRS-2/磷脂酰肌醇3-激酶（PI 3 K）信号传导中的主要缺陷。另一方面，β3-AR激动剂治疗2周后，小鼠开始减轻体重，表明该治疗能够克服IRS-2/PI 3 K信号传导中的主要缺陷并降低体重设定点.Conclusions/interpretationRecovery of acquired leptin resistance does not lead to a resetting of the body weight set point in obese IRS-2/PI 3 K-deficient mice.β3-AR激动剂治疗可能作用于PI 3 K和/或STAT 3远端或独立于PI 3 K和/或STAT 3的某些通路，诱导体重设定点的重置。
Aim/hypothesisLowering the body weight set point is a prerequisite for the maintenance of reduced body weight. In this context, obesity is known to be strongly linked to leptin resistance, and it remains to be clarified whether recovery from leptin resistance might lower the body weight set point to allow sustained body weight loss.MethodsObese IRS-2 knockout (IRS-2−/−) mice were subjected to calorie restriction (CR) or β3-adrenergic receptor (AR) agonist treatment. The physiological effects of leptin, hypothalamic leptin signaling, and alterations of the body weight set point were evaluated.ResultsIn the CR mice, recovery from acquired leptin resistance was observed, as shown by the restoration of the suppressive effects of leptin on food intake and weight gain, as well as the recovery of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Nevertheless, the body weight quickly rebounded to the original body weight after cessation of the CR, suggesting that CR failed to overcome the primary defect in IRS-2/phosphatidylinositol 3-kinase (PI3K) signaling. On the other hand, after 2 weeks β3-AR agonist treatment, the mice began to lose body weight, indicating that the treatment was able to overcome the primary defect in IRS-2/PI3K signaling and lower the body weight set point.Conclusions/interpretationRecovery of acquired leptin resistance does not lead to a resetting of the body weight set point in obese IRS-2/PI3K-defective mice. β3-AR agonist treatment may act on some pathways distal to or independent of PI3K and/or STAT3, inducing resetting of the body weight set point.