Clara 2016 Metabolism

Clara R, Langhans W, Mansouri A (2016) Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis. Metabolism 65:8-17.

» https://www.ncbi.nlm.nih.gov/pubmed/26892511

Clara R, Langhans W, Mansouri A (2016) Metabolism

Abstract: OBJECTIVE:

Glucagon-like peptide-1 (GLP-1) is a potent satiating and incretin hormone released by enteroendocrine L-cells in response to eating. Dietary fat, in particular monounsaturated fatty acids, such as oleic acid (OA), potently stimulates GLP-1 secretion from L-cells. It is, however, unclear whether the intracellular metabolic handling of OA is involved in this effect. METHODS:

First we determined the optimal medium for the bioenergetics measurements. Then we examined the effect of OA on the metabolism of the immortalized enteroendocrine GLUTag cell model and assessed GLP-1 release in parallel. We measured oxygen consumption rate and extracellular acidification rate in response to OA and to different metabolic inhibitors with the Seahorse extracellular flux analyzer. RESULTS:

OA increased cellular respiration and potently stimulated GLP-1 release. The fatty acid oxidation inhibitor etomoxir did neither reduce OA-induced respiration nor affect the OA-induced GLP-1 release. In contrast, inhibition of the respiratory chain or of downstream steps of aerobic glycolysis reduced the OA-induced GLP-1 release, and an inhibition of the first step of glycolysis by addition of 2-deoxy-d-glucose even abolished it. CONCLUSION:

These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1. • Keywords: GLP-1, GLUTag cells, Seahorse extracellular flux analyzer, Oxygen consumption rate, Extracellular acidification rate • Bioblast editor: Garcia-Souza LF

Labels: MiParea: Respiration

Organism: Mouse

Notes/Quotes

400 uM Etomoxir used in the experiments. Strong inhibition of respiration in the abscence of oleic acid in Fig. 3A.
"Etomoxir Reduced Cell Respiration but had No Effect on GLP-1 Release"
"Treatment of the cells with Eto, a potent blocker of CPT-1 [29], reduced cellular respiration by almost 40% in control and OAstimulated cells. The remaining respiration indicates, however, that the mFAO was not the only contributor to oxygen consumption under these conditions."