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J Exp Biol. 2017 Apr 1;220(Pt 7):1187-1191. doi: 10.1242/jeb.150805. Epub 2017 Jan 19.

Central metabolic sensing remotely controls nutrient-sensitive endocrine response in Drosophila via Sir2/Sirt1-upd2-IIS axis.

Author information

1
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
2
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India ullas@tifr.res.in.

Abstract

Endocrine signaling is central in coupling organismal nutrient status with maintenance of systemic metabolic homeostasis. While local nutrient sensing within the insulinogenic tissue is well studied, distant mechanisms that relay organismal nutrient status in controlling metabolic-endocrine signaling are less well understood. Here, we report a novel mechanism underlying the distant regulation of the metabolic endocrine response in Drosophila melanogaster We show that the communication between the fat body and insulin-producing cells (IPCs), important for the secretion of Drosophila insulin-like peptides (dILPs), is regulated by the master metabolic sensor Sir2/Sirt1. This communication involves a fat body-specific direct regulation of the JAK/STAT cytokine upd2 by Sir2/Sirt1. We have also uncovered the importance of this regulation in coupling nutrient inputs with dILP secretion, and distantly controlling insulin/IGF signaling (IIS) in the intestine. Our results provide fundamental mechanistic insights into the top-down control involving tissues that play key roles in metabolic sensing, endocrine signaling and nutrient uptake.

KEYWORDS:

DILP secretion; Insulin secretion; Insulin signaling; Intestine; JAK/STAT ligand; Metabolic homeostasis; Metabolism; NAD+ sensor; Nutrient sensing

PMID:
28104798
DOI:
10.1242/jeb.150805
[Indexed for MEDLINE]
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