School of Natural Sciences, University of California, Merced, Merced, CA, United States.
Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Front Endocrinol (Lausanne). 2020 Jun 10;11:363. doi: 10.3389/fendo.2020.00363. eCollection 2020.
Caloric restriction, among other behavioral interventions, has demonstrated benefits on improving glycemic control in obesity-associated diabetic subjects. However, an acute and severe intervention without proper maintenance could reverse the initial benefits, with additional metabolic derangements. To assess the effects of an acute caloric restriction in a metabolic syndrome model, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without a 10-day body mass (BM) recovery period, along with their respective controls. An oral glucose tolerance test (oGTT) was performed after CR and BM recovery. Both strains had higher rates of mass gain during recovery vs. controls; however, the regain was partial (ca. 50% of controls) over the measurement period. Retroperitoneal and epididymal adipose masses decreased 30% (8.8 g, < 0.001) in OLETF; however, this loss only accounted for 11.5% of the total BM loss. CR decreased blood glucose AUC 16% in LETO and 19% in OLETF, without significant decreases in insulin. Following CR, hepatic expression of the gluconeogenic enzyme, PEPCK, was reduced 55% in OLETF compared to LETO, and plasma triglycerides (TG) decreased 86%. Acute CR induced improvements in glucose tolerance and TG suggestive of improvements in metabolism; however, partial recovery of BM following CR abolished the improvement in glucose tolerance. The present study highlights the importance of proper maintenance of BM after CR as only partial recovery of the lost BM reversed benefits of the initial mass loss.
热量限制等行为干预措施已被证明可改善肥胖相关糖尿病患者的血糖控制。然而,没有适当维持的急性和剧烈干预可能会逆转初始益处,并导致额外的代谢紊乱。为了评估急性热量限制对代谢综合征模型的影响,我们对 15 周龄的 Long Evans Tokushima Otsuka (LETO) 和 Otsuka Long Evans Tokushima Fatty (OLETF) 大鼠进行了热量限制(CR:50%×10 天),其中一些大鼠在热量限制后有 10 天的体重(BM)恢复期,同时设置了各自的对照组。在 CR 和 BM 恢复后进行口服葡萄糖耐量试验(oGTT)。与对照组相比,两种品系在恢复期间的体重增加率都更高;然而,在测量期间,体重的恢复是部分的(约为对照组的 50%)。OLETF 大鼠的腹膜后和附睾脂肪质量减少了 30%(8.8g,<0.001);然而,这种损失仅占 BM 总损失的 11.5%。CR 使 LETO 大鼠的血糖 AUC 降低了 16%,使 OLETF 大鼠的血糖 AUC 降低了 19%,而胰岛素没有显著降低。在 CR 后,OLETF 大鼠的肝源性糖异生酶 PEPCK 的表达降低了 55%,而 LETO 大鼠的表达没有变化,同时血浆甘油三酯(TG)降低了 86%。急性 CR 改善了葡萄糖耐量和 TG,提示代谢改善;然而,CR 后 BM 的部分恢复消除了对葡萄糖耐量改善的影响。本研究强调了 CR 后适当维持 BM 的重要性,因为只有部分恢复丢失的 BM 才能逆转初始体重减轻的益处。