Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila

Abstract

Nutritional condition during the juvenile growth period considerably affects final adult size. The insulin/insulin-like growth factor signaling (IIS)/target of rapamycin (TOR) nutrient-sensing pathway is known to regulate growth and metabolism in response to nutritional conditions. However, there is limited information on how endocrine pathways communicate nutritional information to different metabolic organs to regulate organismal growth. Here, we show that Imaginal morphogenesis protein-Late 2 (Imp-L2), a homolog of insulin-like growth factor-binding protein 7 (IGFBP7), plays a key role in the nutritional control of organismal growth. Nutritional restriction during the larval growth period causes undersized adults, which is largely diminished by mutation. We delineate a pathway in which nutritional restriction increases levels of the steroid hormone ecdysone, which, in turn, triggers ecdysone signaling-dependent Imp-L2 production from the fat body, a fly adipose organ, thereby attenuating peripheral IIS and body growth. Surprisingly, this endocrine pathway operates independent of the fat-body-TOR internal nutrient sensor, long believed to be the control center for nutrition-dependent growth. Our study reveals a previously unrecognized endocrine circuit mediating nutrition-dependent juvenile growth, which could also potentially be related to the insulin resistance frequently observed in puberty.

Expression profiling of winged‐ and wingless‐destined pea aphid embryos implicates insulin/insulin growth factor signaling in morph differences

“…The relationship between ecdysone and insulin signaling has been well elucidated in Drosophila , where ecdysone synthesis by the prothoracic gland is positively regulated by insulin‐signaling via FoxO (Koyama, Rodrigues, Athanasiadis, Shingleton, & Mirth, ), while ecdysone‐signaling in the fat body remotely suppresses the release of insulin‐like peptides from neurosecretory cells of the brain (Colombani et al, ). The activity of circulating insulin is further suppressed by the ecdysone‐regulated synthesis of insulin‐binding proteins impl2 (Honegger et al, ; Lee et al, ), which we found is at significantly higher levels in putatively wingless versus winged aphid embryos (Figure ). Thus, it is possible that the observed suppression of insulin‐signaling in embryos destined to be wingless is a consequence of elevated ecdysone signaling through maternally provided ecdysone (hypothesized relationship illustrated in Figure ).…”

Serotonin signaling regulates insulin-like peptides for growth, reproduction, and metabolism in the disease vector Aedes aegypti

“…Both energy resources acquired for juvenile growth and the timing of feeding cessation during the final larval instar are critical to the final adult body-size determination (36,37). Thus, we used the fifth-day fourth-instar larva when it stops feeding (wandering stage) as a checkpoint to determine the larval body size.…”

Growth and Maturation in Development: A Fly’s Perspective

“…This increased circulating ecdysone level activates EcR in the fat body and upregulates the production of the IGF-binding partner (IGF-BP) ImpL2. Consequently, Imp-L2 binds to and inactivates the circulating DILPs attenuating peripheral IIS and body growth [52]. Third, by repressing miRNA mir8, the rise of ecdysone titers upregulates the mir8 target U-shaped which is a negative regulator of insulin signaling [53].…”