Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin
Peptide YY levels are decreased by fasting and elevated following caloric intake but are not regulated by leptin
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DOI：
10.1007/s00125-005-0041-2
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发表时间：
2006-01-01
期刊：
影响因子：
8.2
通讯作者：
Mantzoros, CS
中科院分区：
文献类型：
--
作者：
Chan, JL;Stoyneva, V;Mantzoros, CS
目的/假设：肽YY（PYY）是一种肠源性激素，已显示可减少动物和人类的短期食物摄入。已经提出PYY的缺乏导致人类肥胖。然而，PYY调节的生理因素，如热量限制，或其他重要的分子在能量稳态，如瘦素，仍有待充分阐明。材料与方法：我们评估了以下因素对PYY水平的影响：（1）5名健康正常体重受试者的热量摄入（混合餐）;（2）8名瘦男性和7名瘦女性分别禁食2天或3天;（3）生理替代剂量和药理剂量的重组人瘦素给药。结果如下：混合餐后PYY水平增加50%（p=0.01），短期完全禁食2或3天将瘦素和PYY水平分别降低至基线的20-30%和40-60%（均p < 0.05）。然而，重组人瘦素管理在生理剂量，以恢复禁食诱导的瘦素水平的下降，并在短期内在药理剂量对PYY水平没有影响。结论/解释：PYY在进食后增加，在禁食后减少，其方式与能量稳态的膳食相关信号一致。重要的是，这种肠道分泌分子的循环水平在短期内不受瘦素的调节。这些发现有助于我们理解调节人类食欲的稳态系统，包括胃肠分泌和脂肪细胞分泌信号的可能冗余。这可能对未来治疗肥胖症的药物开发具有重要意义。
Aims/hypothesis: Peptide YY (PYY) is a gut-derived hormone that has been shown to reduce short-term food intake in animals and humans. It has been proposed that deficiency of PYY contributes to obesity in humans. However, the physiology of PYY regulation by factors such as caloric restriction, or by other molecules important in energy homeostasis, e.g. leptin, remains to be fully elucidated. Materials and methods: We evaluated the effect on PYY levels of: (1) caloric ingestion (a mixed meal) in five healthy normal-weight subjects; (2) fasting for 2 or 3 days in eight lean men and seven lean women respectively; and (3) recombinant human leptin administration at physiological replacement and pharmacological doses. Results: PYY levels increased 50% after a mixed meal (p=0.01), and short-term complete fasting for 2 or 3 days decreased leptin and PYY levels to 20-30% and 40-60% of baseline, respectively (both p < 0.05). However, recombinant human leptin administration at physiological doses to restore the fasting-induced decrease of leptin levels and at pharmacological doses over the short term had no effect on PYY levels. Conclusions/interpretation: PYY increases after meal ingestion and decreases after fasting in a manner consistent with a meal-related signal of energy homeostasis. Importantly, circulating levels of this gut-secreted molecule are independent of regulation by leptin over the short term. These findings contribute towards our understanding of the homeostatic systems that regulate appetite in humans, including the possible redundancy of gastrointestinally secreted and adipocyte-secreted signals. This may be of importance for the future development of medications to treat obesity.