title: Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis.
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.
  
  
  CONCLUSIONS
  These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1.
authors.affiliation: Physiology and Behavior Laboratory, ETH Zürich, 8603 Schwerzenbach (Zürich), Switzerland.
authors.forename: Rosmarie
authors.initials: R
authors.lastname: Clara
authors.affiliation: Physiology and Behavior Laboratory, ETH Zürich, 8603 Schwerzenbach (Zürich), Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.affiliation: Physiology and Behavior Laboratory, ETH Zürich, 8603 Schwerzenbach (Zürich), Switzerland. Electronic address: abdelhak-mansouri@ethz.ch.
authors.forename: Abdelhak
authors.initials: A
authors.lastname: Mansouri
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects*; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D019301:Oleic Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D019289:Pyruvic Acid; D052216:Glucagon-Like Peptide 1; D000255:Adenosine Triphosphate; D005947:Glucose
keywords: Extracellular acidification rate; GLP-1; GLUTag cells; Oxygen consumption rate; Seahorse extracellular flux analyzer