Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation

PLoS Biol. 2016 Feb 29;14(2):e1002392. doi: 10.1371/journal.pbio.1002392. eCollection 2016 Feb.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Size
  • Brain / metabolism
  • Culture Techniques
  • Cytokines / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / physiology*
  • Fat Body / metabolism*
  • Female
  • Insulin / metabolism*
  • Insulin Secretion
  • Male
  • Somatomedins / metabolism*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Cytokines
  • Drosophila Proteins
  • Insulin
  • Somatomedins
  • growth-blocking peptide, Drosophila
  • TOR Serine-Threonine Kinases

Grant support

TK is supported by a fellowship from the Fundação para a Ciência e a Tecnologia (SFRH/BPD/74313/2010). This work was funded by the Fundação Calouste Gulbenkian to CKM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.