STIM1 regulates calcium signaling in taste bud cells and preference for fat in mice
Gado Dramane, … , Philippe Besnard, Naim Akhtar Khan
Gado Dramane, … , Philippe Besnard, Naim Akhtar Khan
Published May 1, 2012
Citation Information: J Clin Invest. 2012;122(6):2267-2282. https://doi.org/10.1172/JCI59953.
View: Text | PDF
Research Article Metabolism

STIM1 regulates calcium signaling in taste bud cells and preference for fat in mice

Abstract

Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. The lipid-binding glycoprotein CD36, which is expressed by circumvallate papillae (CVP) of the mouse tongue, has been implicated in oro-gustatory perception of dietary lipids. Here, we demonstrate that stromal interaction molecule 1 (STIM1), a sensor of Ca2+ depletion in the endoplasmic reticulum, mediates fatty acid–induced Ca2+ signaling in the mouse tongue and fat preference. We showed that linoleic acid (LA) induced the production of arachidonic acid (AA) and lysophosphatidylcholine (Lyso-PC) by activating multiple phospholipase A2 isoforms via CD36. This activation triggered Ca2+ influx in CD36-positive taste bud cells (TBCs) purified from mouse CVP. LA also induced the production of Ca2+ influx factor (CIF). STIM1 was found to regulate LA-induced CIF production and the opening of multiple store-operated Ca2+ (SOC) channels. Furthermore, CD36-positive TBCs from Stim1–/– mice failed to release serotonin, and Stim1–/– mice lost the spontaneous preference for fat that was observed in wild-type animals. Our results suggest that fatty acid–induced Ca2+ signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat.

Authors

Gado Dramane, Souleymane Abdoul-Azize, Aziz Hichami, Timo Vögtle, Simon Akpona, Christophe Chouabe, Hassimi Sadou, Bernhard Nieswandt, Philippe Besnard, Naim Akhtar Khan

×

Figure 5

Effect of CIF, AA, and Lyso-PC on Ca2+ influx in CD36-positive TBCs.

Options: View larger image (or click on image) Download as PowerPoint
Effect of CIF, AA, and Lyso-PC on Ca2+ influx in CD36-positive TBCs. (...
(A) Effect of CIF on Ca2+ influx. The experiments were performed in Ca2+-free medium. CIF was purified from LA-treated (CIF) or TG-treated (TG-CIF) CD36-positive TBCs. The arrows indicate when the test molecules, i.e., CaCl2 (1.5 mM) and CIF (50 μl) or CIF-TG (50 μl), were added. (B and C) Histograms of the effects of C-CIF (extracted from control untreated cells), CIF, AA, and Lyso-PC. (D) Activation of La3+-sensitive current by CIF in Jurkat T cells. Mean La3+-sensitive current density-voltage relationships recorded in the absence (open circles, n = 7) or presence (filled circles, n = 9) of CIF included in the pipette solution (1:15 dilution). The inset shows representative ramp membrane currents recorded in response to voltage ramps, of 50-ms duration applied from –100 to +100 mV in a Jurkat T cell dialyzed with the CIF-containing pipette solution in the absence (a) or presence (b) of 20 μM La3+. The difference curves (a and b, in gray) characterize the La3+-sensitive current.