PMID- 34918430
OWN - NLM
STAT- MEDLINE
DCOM- 20220222
LR  - 20220531
IS  - 1365-2443 (Electronic)
IS  - 1356-9597 (Linking)
VI  - 27
IP  - 2
DP  - 2022 Feb
TI  - Sima, a Drosophila homolog of HIF-1alpha, in fat body tissue inhibits larval body 
      growth by inducing Tribbles gene expression.
PG  - 145-151
LID - 10.1111/gtc.12913 [doi]
AB  - 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) alpha 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.
CI  - (c) 2021 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
FAU - Noguchi, Koji
AU  - Noguchi K
AD  - Department of Life Sciences and Medical BioScience, Waseda University School of 
      Advanced Science and Engineering, Tokyo, Japan.
FAU - Yokozeki, Kyosuke
AU  - Yokozeki K
AD  - Department of Life Sciences and Medical BioScience, Waseda University School of 
      Advanced Science and Engineering, Tokyo, Japan.
FAU - Tanaka, Yuko
AU  - Tanaka Y
AD  - Department of Life Sciences and Medical BioScience, Waseda University School of 
      Advanced Science and Engineering, Tokyo, Japan.
FAU - Suzuki, Yasuhiro
AU  - Suzuki Y
AD  - Department of Life Sciences and Medical BioScience, Waseda University School of 
      Advanced Science and Engineering, Tokyo, Japan.
FAU - Nakajima, Kazuki
AU  - Nakajima K
AD  - Department of Life Sciences and Medical BioScience, Waseda University School of 
      Advanced Science and Engineering, Tokyo, Japan.
FAU - Nishimura, Takashi
AU  - Nishimura T
AD  - Laboratory of Metabolic Regulation and Genetics, Institute for Molecular and 
      Cellular Regulation, Gunma University, Gunma, Japan.
FAU - Goda, Nobuhito
AU  - Goda N
AUID- ORCID: 0000-0003-0295-4257
AD  - Department of Life Sciences and Medical BioScience, Waseda University School of 
      Advanced Science and Engineering, Tokyo, Japan.
LA  - eng
GR  - 2013B-174/a Waseda University Grant for Special Research Projects/
GR  - 2014B-313/a Waseda University Grant for Special Research Projects/
GR  - 2015B-323/a Waseda University Grant for Special Research Projects/
GR  - 2611103/a Grant-in-Aid for Scientific Research on Innovative Areas "Oxygen 
      Biology: a new criterion for integrated understanding of life"/
PT  - Journal Article
DEP - 20211227
PL  - England
TA  - Genes Cells
JT  - Genes to cells : devoted to molecular & cellular mechanisms
JID - 9607379
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Sima protein, Drosophila)
RN  - 0 (trbl protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Cell Cycle Proteins/genetics/metabolism
MH  - *DNA-Binding Proteins/genetics/metabolism
MH  - *Drosophila/genetics/growth & development
MH  - *Drosophila Proteins/genetics/metabolism
MH  - Fat Body/metabolism
MH  - Gene Expression
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Larva/growth & development
MH  - *Protein Serine-Threonine Kinases/genetics/metabolism
OTO - NOTNLM
OT  - Tribbles
OT  - HIF-1
OT  - fat body
OT  - insulin signaling
OT  - larval body growth
EDAT- 2021/12/18 06:00
MHDA- 2022/02/23 06:00
CRDT- 2021/12/17 07:24
PHST- 2021/12/13 00:00 [revised]
PHST- 2021/10/11 00:00 [received]
PHST- 2021/12/13 00:00 [accepted]
PHST- 2021/12/18 06:00 [pubmed]
PHST- 2022/02/23 06:00 [medline]
PHST- 2021/12/17 07:24 [entrez]
AID - 10.1111/gtc.12913 [doi]
PST - ppublish
SO  - Genes Cells. 2022 Feb;27(2):145-151. doi: 10.1111/gtc.12913. Epub 2021 Dec 27.