Acylated Ghrelin and The Regulation of Lipid Metabolism in The Intestine

N Auclair,C Garofalo,Y Ou,E Levy,L Melbouci,N Patey,L Magri-Tomaz,A Sané,D H St-Pierre

doi:10.1038/s41598-019-54265-0

Abstract

Acylated ghrelin (AG) is a gastrointestinal (GI) peptide mainly secreted by the stomach that promotes cytosolic lipid droplets (CLD) hypertrophy in adipose tissues and liver. However, the role of AG in the regulation of lipid metabolism in the intestine remains unexplored. This study aimed at determining whether AG influences CLD production and chylomicron (CM) secretion in the intestine. The effects of AG and oleic acid on CLD accumulation and CM secretion were first investigated in cultured Caco-2/15 enterocytes. Intestinal lipid metabolism was also studied in Syrian Golden Hamsters submitted to conventional (CD) or Western (WD) diets for 8 weeks and continuously administered with AG or physiological saline for the ultimate 2 weeks. In cultured Caco-2/15 enterocytes, CLD accumulation influenced CM secretion while AG reduced fatty acid uptake. In WD hamsters, continuous AG treatment amplified chylomicron output while reducing postprandial CLD accumulation in the intestine. The present study supports the intimate relationship between CLD accumulation and CM secretion in the intestine and it underlines the importance of further characterizing the mechanisms through which AG exerts its effects on lipid metabolism in the intestine.

Highlights

The alarming increase in the incidence of obesity is a major issue for social health authorities worldwide
In response to oleic acid (OA), total cytosolic lipid droplets (CLD) area was increased in a dose-response manner (Fig. 1A) while maximal average CLD size was reached at concentrations of 600 and 900 μM (Fig. 1B)
Cytosolic lipid droplets are important organelles containing a core of TAG and cholesteryl ester surrounded by a phospholipid monolayer[23]

Summary

Introduction

The alarming increase in the incidence of obesity is a major issue for social health authorities worldwide. CM production has been shown to be regulated by gut-derived peptides, which are secreted by enteroendocrine cells located throughout tissues of the stomach, small intestine and colon[8] Many of these hormones are key neuroendocrine regulators of vital functions such as eating behaviours, glucose homeostasis, energy expenditure and lipid metabolism. Some of these peptides such as glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), neurotensin and leptin were previously shown to control CLD accumulation and/or CM secretion in the small intestine[9,10,11]. In Syrian Golden Hamsters, AG potently reduced postprandial CLD accruement while enhancing CM output and promoting systemic dyslipidemia

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Conclusion