Glucagon-like peptide-1 Production in the GLUTag Cell Line Is Impaired by Free Fatty Acids via Endoplasmic Reticulum Stress

Metabolism. 2014 Jun;63(6):800-11. doi: 10.1016/j.metabol.2014.02.012. Epub 2014 Feb 25.

Abstract

Objects: Glucagon-like peptide-1 (GLP-1) is secreted from intestinal L cells, enhances glucose-stimulated insulin secretion, and protects pancreas beta cells. However, few studies have examined hypernutrition stress in L cells and its effects on their function. Here, we demonstrated that a high-fat diet reduced glucose-stimulated secretion of GLP-1 and induced expression of an endoplasmic reticulum (ER) stress markers in the intestine of a diet-induced obesity mouse model.

Methods: To clarify whether ER stress in L cells caused the attenuation of GLP-1 secretion, we treated the mouse intestinal L cell line, GLUTag cells with palmitate or oleate.

Results: Palmitate, but not oleate caused ER stress and decreased the protein levels of prohormone convertase 1/3 (PC1/3), an essential enzyme in GLP-1 production. The same phenomena were observed in GLUTag cells treated with in ER stress inducer, thapsigargin. Moreover, oleate improved palmitate-induced ER stress, reduced protein and activity levels of PC1/3, and attenuated GLP-1 secretion from GLUTag cells.

Conclusions/interpretation: These results suggest that the intake of abundant saturated fatty acids induces ER stress in the intestine and decreases GLP-1 production.

Keywords: ER stress; GLP-1; GLUTag; PC1/3.

MeSH terms

  • Animals
  • Blotting, Western
  • Diet, High-Fat
  • Endoplasmic Reticulum Stress / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Glucagon-Like Peptide 1 / drug effects*
  • Glucagon-Like Peptide 1 / metabolism
  • L Cells / drug effects
  • L Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Obesity / metabolism*
  • Oleic Acid / administration & dosage
  • Oleic Acid / pharmacology*
  • Palmitates / administration & dosage
  • Palmitates / adverse effects*
  • Proprotein Convertase 1 / antagonists & inhibitors*
  • Real-Time Polymerase Chain Reaction
  • Thapsigargin / pharmacology

Substances

  • Enzyme Inhibitors
  • Palmitates
  • Oleic Acid
  • Thapsigargin
  • Glucagon-Like Peptide 1
  • Proprotein Convertase 1