Fatty acid composition in 2-monoacylglycerol modulates GLP-1 secretion

Area of Science:

• Metabolic Regulation
• Endocrinology
• Nutritional Science

Background:

• Glucagon-like peptide-1 (GLP-1) is a crucial intestinal hormone regulating blood glucose, appetite, and beta-cell function.
• Previous research identified 2-oleoylglycerol (2-OG) as a GLP-1 secretagogue.

Purpose of the Study:

• To screen 2-monoacylglycerols (2-MAGs) for enhanced GLP-1 secretion.
• To investigate the receptors involved in 2-palmitoylglycerol (2-PG)-induced GLP-1 release.
• To assess the physiological impact of fatty acid positional distribution in triacylglycerols (TAGs) on GLP-1 secretion.

Main Methods:

• Screening of eight 2-MAGs in STC-1 cells.
• Pharmacological inhibition using G protein-coupled receptor 119 (GPR119) and G protein-coupled receptor 40 (GPR40) antagonists.
• Administration of oils with varying sn-2 fatty acid compositions to mice and measurement of portal vein GLP-1 levels.

Main Results:

• 2-palmitoylglycerol (2-PG) was identified as the most potent enhancer of GLP-1 secretion among tested 2-MAGs.
• 2-PG-induced GLP-1 secretion was attenuated by GPR119 and GPR40 antagonists, indicating GPR40 activation by 2-PG.
• Mice fed oil enriched with sn-2 palmitate showed significantly higher GLP-1 levels compared to those fed sn-2 oleate or sn-1/sn-3 palmitate oils.

Conclusions:

• 2-palmitoylglycerol (2-PG) is a potent enhancer of GLP-1 secretion, acting through GPR119 and GPR40.
• The positional distribution of fatty acids within TAGs critically influences GLP-1 secretion in vivo.
• 2-PG represents a promising target for nutritional strategies aimed at metabolic regulation.