Elsevier

Molecular Metabolism

Volume 3, Issue 7, October 2014, Pages 717-730
Molecular Metabolism

Original article
Altered ghrelin secretion in mice in response to diet-induced obesity and Roux-en-Y gastric bypass

https://doi.org/10.1016/j.molmet.2014.07.009Get rights and content
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open access

Abstract

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.

Keywords

Ghrelin secretion
Obesity
Roux-en-Y gastric bypass
Norepinephrine
Sympathetic nervous system
Glucose

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Vincent Aguirre and Jeffrey M. Zigman contributed equally to this work.