Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
Department of Endocrinology, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
Nutrients. 2021 May 4;13(5):1544. doi: 10.3390/nu13051544.
Sensitization to the adipokine leptin is a promising therapeutic strategy against obesity and its comorbidities and has been proposed to contribute to the lasting metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. We formally tested this idea using Zucker fatty rats as an established genetic model of obesity, glucose intolerance, and fatty liver due to leptin receptor deficiency. We show that the changes in body weight in these rats following RYGB largely overlaps with that of diet-induced obese Wistar rats with intact leptin receptors. Further, food intake and oral glucose tolerance were normalized in RYGB-treated Zucker fatty rats to the levels of lean Zucker fatty controls, in association with increased glucagon-like peptide 1 (GLP-1) and insulin release. In contrast, while fatty liver was also normalized in RYGB-treated Zucker fatty rats, their circulating levels of the liver enzyme alanine aminotransferase (ALT) remained elevated at the level of obese Zucker fatty controls. These findings suggest that the leptin system is not required for the normalization of energy and glucose homeostasis associated with RYGB, but that its potential contribution to the improvements in liver health postoperatively merits further investigation.
对脂肪因子瘦素的敏感是一种有前途的治疗肥胖及其合并症的策略，并被认为有助于罗伊氏 Y 胃旁路（RYGB）手术的持久代谢益处。我们使用 Zucker 肥胖大鼠作为由于瘦素受体缺乏导致肥胖、葡萄糖不耐受和脂肪肝的既定遗传肥胖模型，正式检验了这一观点。我们表明，这些大鼠在 RYGB 后的体重变化与具有完整瘦素受体的饮食诱导肥胖 Wistar 大鼠的体重变化大致重叠。此外，在 RYGB 治疗的 Zucker 肥胖大鼠中，食物摄入和口服葡萄糖耐量恢复到瘦 Zucker 肥胖对照的水平，同时胰高血糖素样肽 1 (GLP-1) 和胰岛素释放增加。相比之下，尽管 RYGB 治疗也使肥胖 Zucker 肥胖大鼠的脂肪肝正常化，但它们循环中的丙氨酸氨基转移酶 (ALT) 水平仍保持在肥胖 Zucker 肥胖大鼠的水平。这些发现表明，在 RYGB 相关的能量和葡萄糖稳态正常化中不需要瘦素系统，但它对术后肝脏健康改善的潜在贡献值得进一步研究。
