TY - JOUR
T1 - 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
AU - Senda, Satoko
AU - Inoue, Atsushi
AU - Mahmood, Arshad
AU - Suzuki, Ryo
AU - Kamei, Nozomu
AU - Kubota, Naoto
AU - Watanabe, Taku
AU - Aoyama, Masashi
AU - Nawaz, Allah
AU - Ohkuma, Yoshiaki
AU - Tsuneyama, Koichi
AU - Koshimizu, Yukiko
AU - Usui, Isao
AU - Saeki, Kumiko
AU - Kadowaki, Takashi
AU - Tobe, Kazuyuki
N1 - Publisher Copyright:
© 2015, The Japan Diabetes Society.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Aim/hypothesis: Lowering 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. Methods: Obese 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. Results: In 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/interpretation: Recovery 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.
AB - Aim/hypothesis: Lowering 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. Methods: Obese 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. Results: In 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/interpretation: Recovery 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.
KW - Body weight set point
KW - Calorie restriction
KW - IRS-2 mice
KW - Leptin resistance
KW - Signal transducer and activator of transcription 3 (STAT3)
KW - β3-adrenergic receptor agonist
UR - http://www.scopus.com/inward/record.url?scp=84949234139&partnerID=8YFLogxK
U2 - 10.1007/s13340-015-0205-3
DO - 10.1007/s13340-015-0205-3
M3 - 学術論文
AN - SCOPUS:84949234139
SN - 2190-1678
VL - 6
SP - 321
EP - 335
JO - Diabetology International
JF - Diabetology International
IS - 4
ER -