School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.
Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Neuroendocrinology. 2022;112(2):174-185. doi: 10.1159/000515960. Epub 2021 Mar 18.
Dysregulation of metabolic regulatory hormones often occurs during the progress of obesity. Key regulatory hormone insulin-growth hormone (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.
TRF was performed in an over-eating melanocortin 4 receptor-knockout (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 the 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 expressions were measured in terminal liver and subcutaneous white adipose tissues.
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.
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.
代谢调节激素的失调通常发生在肥胖进展过程中。最近提出，关键调节激素胰岛素-生长激素（GH）平衡有助于维持代谢谱。限时喂养（TRF）是一种对抗肥胖的有效策略，但关于脉冲式 GH 释放模式的详细研究还很少。
使用正常食物在过度进食的黑皮质素 4 受体敲除（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，以进行 6 小时脉冲式 GH 谱、葡萄糖耐量试验和胰岛素耐量试验。在第 6 周通过 Phenomaster 系统进行 1 周间接热量测定，通过核磁共振波谱（NMR）测量身体成分。测量终末肝脏和皮下白色脂肪组织中与底物和能量代谢相关的基因表达。
TRF 增加了 MC4RKO 肥胖小鼠暗期脉冲式 GH 的分泌，并抑制了高胰岛素血症，从而降低了胰岛素/ GH 比值。这伴随着胰岛素敏感性、代谢灵活性、葡萄糖耐量的改善，以及葡萄糖波动的减少，同时适当改变了参与底物代谢和脂肪组织褐变的基因表达。NMR 测量显示，TRF 减少了脂肪量，但增加了瘦体重。间接热量计记录表明，TRF 降低了在光期消耗更多脂肪酸以产生能量的呼吸交换率（RER），并增加了暗期活动期间的耗氧量。
TRF 有效降低了过度进食肥胖小鼠的高胰岛素血症，恢复了脉冲式 GH 的分泌，显著改善了底物和能量代谢以及身体成分，而不减少总热量摄入。
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