Abstract Background Dysregulation of metabolic regulatory hormones often occurs during the progress of obesity. Key regulatory hormone Insulin-GH balance has recently been proposed to maintain metabolism profiles. Time-restricted feeding (TRF) is an effective strategy against obesity without detailed research on pulsatile GH releasing patterns. Methods TRF was performed in an over-eating MC4RKO obese mouse model using normal food. Body weight and food intake were measured. Series of blood samples were collected for 6 h pulsatile GH profile, glucose tolerance test and insulin tolerance test at 5, 8, and 9 weeks of TRF, respectively. Indirect calorimetric recordings were performed by Phenomaster system at 6 weeks for 1 week and body composition was measured by Nuclear magnetic resonance spectroscopy (NMR). Substrate and energy metabolism related gene expression were measured in terminal liver and subcutaneous white adipose tissues. Results TRF increased pulsatile GH secretion in dark phase and suppressed hyperinsulinemia in MC4RKO obese mice to reach a reduced insulin/GH ratio. This was accompanied by the improvement in insulin sensitivity, metabolic flexibility, glucose tolerance and decreased glucose fluctuation, together with appropriate modification of gene expression involved in substrate metabolism and adipose tissue browning. NMR measurement showed that TRF decreased fat mass but increased lean mass. Indirect calorimeter recording indicated that TRF decreased the respiratory exchange ratio (RER) reflecting consumption of more fatty acid in energy production in light phase and increased the oxygen consumption during activities in dark phase. Conclusions TRF effectively decreases hyperinsulinemia and restores pulsatile GH secretion in the overeating obese mice with significant improvement in substrate and energy metabolism and body composition without reducing total caloric intake.


中文翻译：

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限时喂养恢复了 MC4RKO 肥胖小鼠的胰岛素生长激素平衡并改善了底物和能量代谢

摘要背景代谢调节激素的失调经常发生在肥胖的进展过程中。最近提出了关键的调节激素胰岛素-GH 平衡来维持代谢曲线。限时喂养 (TRF) 是一种有效的抗肥胖策略，无需对脉动 GH 释放模式进行详细研究。方法在正常饮食的暴食MC4RKO肥胖小鼠模型中进行TRF。测量体重和食物摄入量。分别在 TRF 的第 5、8 和 9 周收集一系列血液样本进行 6 小时的脉动 GH 曲线、葡萄糖耐量试验和胰岛素耐量试验。Phenomaster 系统在 6 周进行 1 周的间接量热记录，并通过核磁共振波谱 (NMR) 测量身体成分。在终末肝脏和皮下白色脂肪组织中测量底物和能量代谢相关基因的表达。结果 TRF 在 MC4RKO 肥胖小鼠中增加了暗期的搏动性 GH 分泌并抑制了高胰岛素血症，从而达到降低的胰岛素/GH 比率。这伴随着胰岛素敏感性、代谢灵活性、葡萄糖耐量和葡萄糖波动降低的改善，以及参与底物代谢和脂肪组织褐变的基因表达的适当修改。NMR 测量表明，TRF 减少了脂肪量，但增加了瘦肉量。间接热量计记录表明，TRF 降低了呼吸交换比（RER），反映了在光相能量产生过程中消耗更多的脂肪酸，并增加了暗相活动过程中的氧消耗。