Cardiovascular, Renal & Metabolic Diseases, MedImmune, Gaithersburg, MD 20878, USA.
Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Nutrients. 2019 Mar 10;11(3):585. doi: 10.3390/nu11030585.
BACKGROUND/GOALS: The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight.
Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet.
Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice.
PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.
背景/目的：肠道 L 细胞分泌的肠肽 YY（PYY）通过脑和外周的 Y2 受体（Y2R）信号传导在饱腹感机制中起作用，是介导减肥手术对食欲和体重有益影响的主要候选物。
在这里，我们评估了 Y2R 信号在对低脂和高脂肪饮食的反应中的作用及其在 Roux-en-Y 胃旁路（RYGB）手术对体重、身体成分、食物摄入、能量消耗和葡萄糖处理的影响中的作用，在全身性 Y2R 缺陷（Y2RKO）和野生型（WT）肥胖的高脂肪饮食的小鼠中。
雄性和雌性 Y2RKO 小鼠在低脂和高脂肪饮食方面的体重、身体成分、空腹血糖和胰岛素水平以及葡萄糖和胰岛素耐量方面的反应正常，直到 30 周龄。与预期相反，肥胖的 Y2RKO 小鼠在手术后 20 周内对 RYGB 的反应与 WT 小鼠相似，初始食欲减退，持续体重减轻，空腹胰岛素、葡萄糖耐量、胰岛素抵抗（HOMA-IR）和肝重显著改善与假手术组相比。此外，与 RYGB 相匹配的非手术性 Y2RKO 小鼠在血糖控制方面表现出与 RYGB 的 Y2RKO 小鼠相似的改善，与 WT 小鼠相似。
在这种全身性基因敲除小鼠模型中，PYY 通过 Y2R 的信号传导对于 RYGB 的正常抑制食欲和降低体重的作用不是必需的。PYY 信号传导通过其他受体亚型或其他肠道饱腹感激素（如胰高血糖素样肽-1（GLP-1））的潜在代偿适应仍有待研究。
