Satiety perception is critical for maintaining energy homeostasis, yet the precise neuroendocrine circuits encoding nutritional state remain elusive. Caenorhabditis elegans allows the determination of neural circuits with a resolution difficult to achieve in other models. Previous work from our laboratory delineated the circuits mediating elevated food intake after fasting, establishing that serotonin and tyramine—the invertebrate counterpart of adrenaline—are crucial for this behavior; however, how the nervous system senses nutritional status remains unknown.
We mapped robust expression of mgl-2, an ortholog of mammalian metabotropic glutamate receptors, to core neurons of the feeding circuit. Here, we demonstrate that mgl-2 mutants are insensitive to satiety, establishing a novel genetic model of hyperphagia. These animals exhibit an increased food intake that closely mimics post-starvation responses. As a consequence, they show enhanced lipid accumulation. Notably, serotonin depletion abolishes this increased food intake in mgl-2 mutants, showing a strict requirement for serotonergic signaling in this response.
We are currently interrogating the activity of key serotonergic and tyraminergic nodes to determine how MGL-2 modulates these pathways. Collectively, our findings reveal that MGL-2 acts as a key receptor for sensing satiety, positioning this receptor as a critical node in the serotonergic network governing feeding behavior.