Fatty acid responses in an enteroendocrine cell line: chemosensory cues for dietary fat.

Abstract

Nutrient-induced stimulation of enteroendocrine cells (EECs) in the small intestine leads to release of the hormones glucagon-like peptide-1 and cholecystokinin that contribute to satiety. Our research has been focusing on the mechanisms that underlie the ability of fat to stimulate enteroendocrine cells during food intake. Recently, using RT-PCR we identified a rich array of potential fatty acid (FA)-activated proteins in the enteroendocrine cell line STC-1 including FA-sensitive potassium channels and several FA-activated G protein coupled receptors (GPCRs) including the long-chain FA-activated receptors GPR40 and GPR120 and the short chain FA-activated receptors, GPR41 and GPR43. To explore functional responses to FAs in STC-1 cells, we have undertaken a series of experiments using Ca 2+ imaging with the ratiometric Ca 2+ indicator, fura-2. Long chain unsaturated FAs elicit concentration-dependent increases in intracellular Ca 2+ in STC-1 cells. Using pharmacological approaches to explore the route for FA-induced Ca 2+ changes, our data are consistent with the interpretation that Ca 2+ influx through voltage-gated Ca 2+ channels and not release from intracellular stores is the major source of Ca 2+ change. In addition, removal of extracellular Na+ also reduces the magnitude of the FA response suggesting that Ca 2+ -activated cation channels may contribute to the depolarization that occurs in the FA transduction pathway. We will present a model based upon available data linking GPCRs, cation channels, potassium channels and voltage-gated Ca 2+ channels in the chemosensory responses of EECs to FAs. Supported by NIH-DK-59611 and International Flavors & Fragrances (TAG).