Iepsen Eva W, Lundgren Julie, Holst Jens J, Madsbad Sten, Torekov Signe S
Department of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark The Novo Nordisk Foundation Center for Basic Metabolic ResearchFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of EndocrinologyHvidovre University Hospital, Hvidovre, Denmark.
Eur J Endocrinol. 2016 Jun;174(6):775-84. doi: 10.1530/EJE-15-1116. Epub 2016 Mar 14.
The hormones glucagon-like peptide 1 (GLP-1), peptide YY3-36 (PYY3-36), ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon have all been implicated in the pathogenesis of obesity. However, it is unknown whether they exhibit adaptive changes with respect to postprandial secretion to a sustained weight loss.
The study was designed as a longitudinal prospective intervention study with data obtained at baseline, after 8 weeks of weight loss and 1 year after weight loss.
Twenty healthy obese individuals obtained a 13% weight loss by adhering to an 8-week very low-calorie diet (800kcal/day). After weight loss, participants entered a 52-week weight maintenance protocol. Plasma levels of GLP-1, PYY3-36, ghrelin, GIP and glucagon during a 600-kcal meal were measured before weight loss, after weight loss and after 1 year of weight maintenance. Area under the curve (AUC) was calculated as total AUC (tAUC) and incremental AUC (iAUC).
Weight loss was successfully maintained for 52 weeks. iAUC for GLP-1 increased by 44% after weight loss (P<0.04) and increased to 72% at week 52 (P=0.0001). iAUC for PYY3-36 increased by 74% after weight loss (P<0.0001) and by 36% at week 52 (P=0.02). tAUC for ghrelin increased by 23% after weight loss (P<0.0001), but at week 52, the increase was reduced to 16% compared with before weight loss (P=0.005). iAUC for GIP increased by 36% after weight loss (P=0.001), but returned to before weight loss levels at week 52. Glucagon levels were unaffected by weight loss.
Meal responses of GLP-1 and PYY3-36 remained increased 1 year after weight maintenance, whereas ghrelin and GIP reverted toward before-weight loss values. Thus, an increase in appetite inhibitory mechanisms and a partly decrease in appetite-stimulating mechanisms appear to contribute to successful long-term weight loss maintenance.
胰高血糖素样肽1（GLP-1）、肽YY3-36（PYY3-36）、胃饥饿素、葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素等激素均与肥胖的发病机制有关。然而，它们在餐后分泌方面是否会随着体重持续减轻而出现适应性变化尚不清楚。
本研究设计为一项纵向前瞻性干预研究，在基线、体重减轻8周后和体重减轻1年后获取数据。
20名健康肥胖个体通过坚持8周极低热量饮食（800千卡/天）实现了13%的体重减轻。体重减轻后，参与者进入为期52周的体重维持方案。在体重减轻前、体重减轻后和体重维持1年后，测量600千卡餐食期间血浆中GLP-1、PYY3-36、胃饥饿素、GIP和胰高血糖素的水平。曲线下面积（AUC）计算为总AUC（tAUC）和增量AUC（iAUC）。
体重减轻成功维持了52周。体重减轻后，GLP-1的iAUC增加了44%（P<0.04），在第52周时增加到72%（P=0.0001）。体重减轻后，PYY3-36的iAUC增加了74%（P<0.0001），在第52周时增加了36%（P=0.02）。体重减轻后，胃饥饿素的tAUC增加了23%（P<0.0001），但在第52周时，与体重减轻前相比，增加幅度降至16%（P=0.005）。体重减轻后，GIP的iAUC增加了36%（P=0.001），但在第52周时恢复到体重减轻前的水平。胰高血糖素水平不受体重减轻的影响。
体重维持1年后，GLP-1和PYY3-36的进餐反应仍保持增加，而胃饥饿素和GIP则恢复到体重减轻前的值。因此，食欲抑制机制的增加和食欲刺激机制的部分降低似乎有助于成功长期维持体重减轻。
