Expression of Serum Retinol Binding Protein and Transthyretin within Mouse Gastric Ghrelin Cells

Angela K Walker,Ichiro Sakata,Zhi Gong,Won-Mee Park,Jeffrey M Zigman

doi:10.1371/journal.pone.0064882

Angela K Walker, Ichiro Sakata + Show 3 more

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https://doi.org/10.1371/journal.pone.0064882

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Abstract

Ghrelin is an orexigenic peptide hormone produced mainly by a distinct group of dispersed endocrine cells located within the gastric oxyntic mucosa. Besides secreted gene products derived from the preproghrelin gene, which include acyl-ghrelin, desacyl-ghrelin and obestatin, ghrelin cells also synthesize the secreted protein nesfatin-1. The main goal of the current study was to identify other proteins secreted from ghrelin cells. An initial gene chip screen using mRNAs derived from highly enriched pools of mouse gastric ghrelin cells demonstrated high levels of serum retinol-binding protein (RBP4) and transthyretin (TTR), both of which are known to circulate in the bloodstream bound to each other. This high expression was confirmed by quantitative RT-PCR using as template mRNA derived from the enriched gastric ghrelin cell pools and from two ghrelin-producing cell lines (SG-1 and PG-1). RBP4 protein also was shown to be secreted into the culture medium of ghrelin cell lines. Neither acute nor chronic caloric restriction had a significant effect on RBP4 mRNA levels within stomachs of C57BL/6J mice, although both manipulations significantly decreased stomach TTR mRNA levels. In vitro studies using PG-1 cells showed no effect on RBP4 release of octanoic acid, epinephrine or norepinephrine, all of which are known to act directly on ghrelin cells to stimulate ghrelin secretion. These data provide new insights into ghrelin cell physiology, and given the known functions of RBP4 and TTR, support an emerging role for the ghrelin cell in blood glucose handling and metabolism.

Highlights

The gastrointestinal tract is home to numerous endocrine cell types, the hormonal products of which play critical roles in several physiologic processes and behaviors, including eating, energy homeostasis, glucose metabolism, and gastrointestinal motility [1,2]
Because retinol binding protein 4 (RBP4) is known to circulate in the bloodstream bound to transthyretin (TTR), we searched the gene chip for TTR mRNA and found its signal intensity to be increased in the humanized Renilla reniformis green fluorescent protein (hrGFP)/ghrelin cell-enriched pools
We describe for the first time marked expression within gastric ghrelin cells of the secreted proteins RBP4 and TTR

Summary

Introduction

The gastrointestinal tract is home to numerous endocrine cell types, the hormonal products of which play critical roles in several physiologic processes and behaviors, including eating, energy homeostasis, glucose metabolism, and gastrointestinal motility [1,2]. Ghrelin is one such gastrointestinal product that is unique in that it is the only known peptide hormone produced in the periphery that potently stimulates food intake [3]. Prior to the discovery of ghrelin, these cells had been identifiable due to their characteristic round, compact, electron-dense secretory granules [18,19,21,22]

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