Data from: To eat or not to eat: ontogeny of hypothalamic feeding controls and a role for leptin in modulating life history transition in amphibian tadpoles

Many animal life histories entail changing feeding ecology, but the molecular bases for these transitions are poorly understood. The amphibian tadpole is typically a growth and dispersal life history stage. Tadpoles are primarily herbivorous, and they capitalize on growth opportunities to reach a minimum body size to initiate metamorphosis. During metamorphic climax, feeding declines, at which time the gastrointestinal tract remodels to accommodate the carnivorous diet of the adult frog. Here we show that anorexigenic hypothalamic feeding controls are absent in the tadpole, but develop during metamorphosis concurrent with the production of the satiety signal leptin. Before metamorphosis there is a large increase in leptin mRNA in fat tissue. Leptin receptor mRNA increased during metamorphosis in the preoptic area/hypothalamus, the key brain region involved with the control of food intake and metabolism. This corresponded with an increase in functional leptin receptor, as evidenced by induction of socs3 mRNA and phosphorylated STAT3 immunoreactivity, and suppression of feeding behavior after injection of recombinant frog leptin. Furthermore, we found that immuno-neutralization of leptin in tadpoles at metamorphic climax caused them to resume feeding. The absence of negative regulation of food intake in the tadpole allows the animal to maximize growth prior to metamorphosis. Maturation of leptin-responsive neural circuits suppresses feeding during metamorphosis to facilitate remodeling of the gastrointestinal tract.

诸多动物的生活史均伴随摄食生态的转变，但此类转变的分子基础仍鲜有解析。两栖类蝌蚪通常属于生长与扩散型生活史阶段，多以植食性为生，借此充分利用生长契机达到最小体型阈值以启动变态发育。在变态高峰期，蝌蚪的摄食活动逐渐减弱，此时胃肠道发生重塑，以适配成蛙的肉食性食谱。本研究证实，蝌蚪体内缺乏厌食性下丘脑摄食调控通路（anorexigenic hypothalamic feeding controls），该通路会在变态发育过程中随饱感信号瘦素（leptin）的产生而逐步成熟。变态发生前，脂肪组织中的瘦素mRNA水平显著升高；视前区/下丘脑——调控摄食与代谢的关键脑区——内的瘦素受体mRNA水平在变态过程中持续上升，这与功能性瘦素受体的表达增加相吻合：注射重组蛙瘦素后，可诱导细胞因子信号抑制因子3（socs3）mRNA的表达与磷酸化STAT3免疫反应性，并抑制蝌蚪的摄食行为。此外，本研究发现，在变态高峰期对蝌蚪体内的瘦素进行免疫中和，可使其恢复摄食活动。蝌蚪体内缺乏摄食负调控机制，使其能够在变态前最大化生长；而响应瘦素的神经环路的成熟，则会在变态过程中抑制摄食，以促进胃肠道的重塑。