IMPACT OF CALCIUM SIGNALING IN CARDIAC AND LIPID-TASTING CELLS: TOWARD AN INTEGRATED UNDERSTANDING OF GENETIC, METABOLIC, AND BEHAVIORAL MECHANISMS ASSOCIATED WITH OBESITY

The concept of the "calcium clock" is particularly applied to cardiac cells where rhythmic responses that rely on fast cycles of calcium release and reuptake, with minimal reliance on STIM/Orai. But it is interesting to see to what extent this concept could also apply to lipid taste cells where sustained calcium support through SOCE is critical for maintaining the ability to detect lipids, facilitated by STIM and Orai. In lipid taste cells, there is no true "calcium clock" comparable to that of cardiac pacemaker cells, because taste cells do not generate autonomous rhythmic depolarizations or action potentials on a regular basis. However, transient calcium oscillations can be observed in response to repeated or prolonged lipid stimulation. These oscillations are largely supported by the SOCE mechanism (involvement of STIM and Orai) and by calcium release via IP3 receptors, but they do not form an involved "clock" capable of generating an autonomous rhythm. . In other words, although calcium is repeatedly mobilized in taste cells in response to fatty acids, these cells do not depend on autonomous calcium fluctuations for their function. Calcium regulation in lipid taste cells is stimulated by an external signal (the presence of fatty acids), whereas the "calcium clock" of cardiac cells is self-sustaining and motivated. Although lipid taste cells do not have an autonomous calcium clock, they exhibit a form of adaptive calcium regulation, particularly in response to repeated or prolonged exposure to dietary lipids. This adaptive regulation relies on calcium plasticity, where adjustments in intracellular calcium via STIM/Orai and IP3 maintain sensitivity to lipid stimuli despite changes in dietary fatty acid load. This process could be compared to an "adaptive calcium clock", although it does not meet the criteria of a "calcium clock" in the strict sense. Adaptive calcium regulation may emerge as a compensatory mechanism, where gustatory cells adjust their signaling in response to chronic and elevated fat intake, potentially leading to habituation. In response to ER stress, gustatory cells might upregulate STIM and Orai signaling to counter chronic calcium depletion. This adaptation could alter lipid taste sensitivity and influence eating behaviors by increasing the appetite for fatty foods.