STIM1 regulates calcium signaling in taste bud cells and preference for fat in mice
Gado Dramane, Souleymane Abdoul-Azize, Aziz Hichami, Timo Vögtle, Simon Akpona, Christophe Chouabe, Hassimi Sadou, Bernhard Nieswandt, Philippe Besnard, Naim Akhtar Khan
Gado Dramane, Souleymane Abdoul-Azize, Aziz Hichami, Timo Vögtle, Simon Akpona, Christophe Chouabe, Hassimi Sadou, Bernhard Nieswandt, Philippe Besnard, Naim Akhtar Khan
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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

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Figure 2

PLA2 activity in CD36-positive TBCs.

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PLA2 activity in CD36-positive TBCs. (A and B) The CD36-positive TBCs ...
(A and B) The CD36-positive TBCs (3 × 106) were treated as described in Methods. The cells were incubated with or without SSO (50 μM) for 20 minutes and then treated with LA. For analysis of Ca2+ dependence of PLA2, the Ca2+-containing medium contained CaCl2 (1.2 mM), whereas Ca2+-free medium contained EGTA (2 mM) in place of CaCl2. PLA2 enzyme activity was calculated as described in the kit protocol. *P < 0.001 compared with unstimulated cells (basal); §P < 0.001 compared with LA-treated cells. (C) The TBCs (2 × 106) were labeled for 2 hours with 1.5 μCi 3H-AA and treated or not with PMA (10 nM) plus ionomycin (Iono, 200 nM), TG (5 μM), or LA (20 μM). After washing, the release of 3H-AA was assessed. (D) Effect of PLA2 inhibitors (15 μM BEL, ATK, BPB, and Ar-A for 10 minutes) on LA- and TG-induced release of 3H-AA in TBCs. Data (mean ± SEM) are expressed as percentage of unstimulated cells; *P < 0.001 compared with respective controls. (E) Western blot detection of 4 isoforms of PLA2 in TBCs after transfection with siRNA (sPLA2 IIa, cPLA2 IVc, sPLA2 V, and iPLA2 VIβ). NsiRNA, nontargeting siRNA. Lanes were run on the same gel but were noncontiguous, as indicated by the white line (F) Release of 3H-AA after tranfection of TBCs with the siRNA isoforms mentioned in E. Experiments were performed as in D. Data (mean ± SEM) are expressed as percentage of LA- or TG-stimulated cells; *P < 0.001 compared with respective controls.