Abstract
In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size.
Highlights
The nutritional environment of developing animals can generate dramatic variation in body size and shape, as well as in their developmental time
To address whether GrowthBlocking Peptide (GBP) are humoral signals that convey the level of Target of Rapamycin (TOR) signaling in the fat body to the insulin-producing cells, we first altered TOR signaling in the fat body and assessed the effects on adult body size, as determined by weighing pharate adults immediately prior to eclosion
Using the G-TRACE method [25], which allows us to identify both lineage-traced expression and live Gal4, we found that C7 Gal4 expressed Gal4 strongly in the fat body and salivary glands at 24 h after third larval instar (L3) ecdysis (AL3E) (S1A Fig)
Summary
The nutritional environment of developing animals can generate dramatic variation in body size and shape, as well as in their developmental time. Incorrect regulation of body size has important consequences on the adult animal, impacting its survival and its fitness by altering its fecundity, longevity, and stress resistance [1,2,3,4]. The fat body senses the concentration of intracellular amino acids through the activity of the Target of Rapamycin (TOR) signaling pathway, which in turn regulates the synthesis and secretion of an undescribed humoral factor(s), called the fat-body–derived signal. This signal regulates systemic growth by controlling the synthesis and secretion of insulin-like peptides (ILPs) by the insulin-producing cells of the brain [10]
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