Sulfakinin Signaling Sense Circulating Fructose and Suppresses Food Consumption via Insulin-Like Peptide in...

Feeding in animals is primarily regulated by the internal satiety state. Sulfakinin (Sk) is well known as a satiety signal that inhibits feeding. However, the underlying mechanism activating the Sk release is not yet fully understood, although the Sk for inhibitions of peripheral sensory systems, gustatory sweet and olfactory food smell sensors, were previously described. Here, in further investigations of Sk signaling pathways, we found the upstream and an additional downstream mechanism by using CRISPR/Cas9-mediated gene knockouts for the upstream gustatory receptor, Gr43a, and the downstream sulfakinin receptor 1, SkR1, in the oriental fruit fly. We demonstrated that the increased hemolymph fructose is sensed by GR43a, which activates the Sk signal in the intercerebralis insuline-like peptide (Sk-ILP) cells. The Sk-ILP acts as an autocrine signal activating the insulin-like peptide 5 (ILP5) as the ultimate satiety signal. This study demonstrated a fructose-Gr43a-Sk-SkR1-ILP5 pathway that regulates feeding behavior by sensing nutritional state.