Sima, a Drosophila homolog of HIF-1α, in fat body tissue inhibits larval body growth by inducing Tribbles gene expression

Koji Noguchi, Kyosuke Yokozeki, Yuko Tanaka, Yasuhiro Suzuki, Kazuki Nakajima, Takashi Nishimura, Nobuhito Goda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Limited oxygen availability impairs normal body growth, although the underlying mechanisms are not fully understood. In Drosophila, hypoxic responses in the larval fat body (FB) disturb the secretion of insulin-like peptides from the brain, inhibiting body growth. However, the cell-autonomous effects of hypoxia on the insulin-signaling pathway in larval FB have been underexplored. In this study, we aimed to examine the effects of overexpression of Sima, a Drosophila hypoxia-inducible factor-1 (HIF-1) α homolog and a key component of HIF-1 transcription factor essential for hypoxic adaptation, on the insulin-signaling pathway in larval FB. Forced expression of Sima in FB reduced the larval body growth with reduced Akt phosphorylation levels in FB cells and increased hemolymph sugar levels. Sima-mediated growth inhibition was reversed by overexpression of TOR or suppression of FOXO. After Sima overexpression, larvae showed higher expression levels of Tribbles, a negative regulator of Akt activity, and a simultaneous knockdown of Tribbles completely abolished the effects of Sima on larval body growth. Furthermore, a reporter analysis revealed Tribbles as a direct target gene of Sima. These results suggest that Sima in FB evokes Tribbles-mediated insulin resistance and consequently protects against aberrant insulin-dependent larval body growth under hypoxia.

Original languageEnglish
Pages (from-to)145-151
Number of pages7
JournalGenes to Cells
Volume27
Issue number2
DOIs
Publication statusPublished - 2022 Feb

Keywords

  • HIF-1
  • Tribbles
  • fat body
  • insulin signaling
  • larval body growth

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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