Uchida Aki, Zechner Juliet F, Mani Bharath K, Park Won-Mee, Aguirre Vincent, Zigman Jeffrey M
Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA ; Division of Endocrinology & Metabolism, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA ; Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA ; Division of Digestive and Liver Diseases, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Mol Metab. 2014 Aug 1;3(7):717-30. doi: 10.1016/j.molmet.2014.07.009. eCollection 2014 Oct.
The current study examined potential mechanisms for altered circulating ghrelin levels observed in diet-induced obesity (DIO) and following weight loss resulting from Roux-en-Y gastric bypass (RYGB). We hypothesized that circulating ghrelin levels were altered in obesity and after weight loss through changes in ghrelin cell responsiveness to physiological cues. We confirmed lower ghrelin levels in DIO mice and demonstrated elevated ghrelin levels in mice 6 weeks post-RYGB. In both DIO and RYGB settings, these changes in ghrelin levels were associated with altered ghrelin cell responsiveness to two key physiological modulators of ghrelin secretion - glucose and norepinephrine. In DIO mice, increases in ghrelin cell density within both the stomach and duodenum and in somatostatin-immunoreactive D cell density in the duodenum were observed. Our findings provide new insights into the regulation of ghrelin secretion and its relation to circulating ghrelin within the contexts of obesity and weight loss.
本研究探讨了饮食诱导肥胖（DIO）以及Roux-en-Y胃旁路术（RYGB）导致体重减轻后循环中胃饥饿素水平改变的潜在机制。我们假设，肥胖及体重减轻后循环中胃饥饿素水平的改变是通过胃饥饿素细胞对生理信号反应性的变化实现的。我们证实了DIO小鼠的胃饥饿素水平较低，并证明RYGB术后6周小鼠的胃饥饿素水平升高。在DIO和RYGB两种情况下，胃饥饿素水平的这些变化都与胃饥饿素细胞对胃饥饿素分泌的两个关键生理调节因子——葡萄糖和去甲肾上腺素的反应性改变有关。在DIO小鼠中，观察到胃和十二指肠内胃饥饿素细胞密度增加，以及十二指肠内生长抑素免疫反应性D细胞密度增加。我们的研究结果为肥胖和体重减轻情况下胃饥饿素分泌的调节及其与循环胃饥饿素的关系提供了新的见解。
