Abstract
Hedgehog (Hh) signaling has been shown to regulate multiple developmental processes, however, it is unclear how it regulates lipid metabolism. Here, we demonstrate that Hh signaling exhibits potent activity in Drosophila fat body, which is induced by both locally expressed and midgut-derived Hh proteins. Inactivation of Hh signaling increases, whereas activation of Hh signaling decreases lipid accumulation. The major lipase Brummer (Bmm) acts downstream of Smoothened (Smo) in Hh signaling to promote lipolysis, therefore, the breakdown of triacylglycerol (TAG). We identify a critical Ci binding site in bmm promoter that is responsible to mediate Bmm expression induced by Hh signaling. Genomic mutation of the Ci binding site significantly reduces the expression of Bmm and dramatically decreases the responsiveness to Ci overexpression. Together, our findings provide a model for lipolysis to be regulated by Hh signaling, raising the possibility for Hh signaling to be involved in lipid metabolic and/or lipid storage diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 128-139 |
| Number of pages | 12 |
| Journal | Developmental Biology |
| Volume | 457 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2020 |
Bibliographical note
Funding Information:This study was supported by the National Institutes of Health grants ( R01GM079684 and R35GM131807 ), and was also supported by the Shared Resource Facilities of the University of Kentucky Markey Cancer Center ( P30CA177558 ), and the Imaging Core and Pilot funds from the COBRE ( P20GM121327 ).
Funding Information:
This study was supported by the National Institutes of Health grants (R01GM079684 and R35GM131807), and was also supported by the Shared Resource Facilities of the University of Kentucky Markey Cancer Center (P30CA177558), and the Imaging Core and Pilot funds from the COBRE (P20GM121327).We are grateful to Dr. Duojia Pan for the act?>?CD2?>?Gal4-DsRed strain; Dr. Ronald Kuhnlein for the UAS-BmmWT and UAS-BmmS38A transgenic lines; Dr. Savraj S. Grewal for the cg-Gal4 line; Vienna Drosophila Resource Center (VDRC) and TRiP at Harvard Medical School for fly stocks; Dr. Brian Gebelein for the anti-HNF4 antibody; Dr. Tom Kornberg for the anti-Hh antibody; and the Developmental Studies Hybridoma Bank (DSHB) for the anti-Ci and anti-?-tubulin antibodies. We also thank the Redox Metabolism Shared Resource Facilities of the University of Kentucky Markey Cancer Center (supported by National Cancer Institute grant P30 CA177558, USA). We also thank the Imaging Core Facility of the COBRE (P20 GM121327, USA) for providing the imaging systems. This study was supported by grants from the National Institute of Health (NIH), USA (R01GM079684 and R35GM131807) to J. J.
Funding Information:
We are grateful to Dr. Duojia Pan for the act > CD2 > Gal4-DsRed strain; Dr. Ronald Kuhnlein for the UAS-Bmm WT and UAS-Bmm S38A transgenic lines; Dr. Savraj S. Grewal for the cg-Gal4 line; Vienna Drosophila Resource Center (VDRC) and TRiP at Harvard Medical School for fly stocks; Dr. Brian Gebelein for the anti-HNF4 antibody; Dr. Tom Kornberg for the anti-Hh antibody; and the Developmental Studies Hybridoma Bank (DSHB) for the anti-Ci and anti-β-tubulin antibodies. We also thank the Redox Metabolism Shared Resource Facilities of the University of Kentucky Markey Cancer Center (supported by National Cancer Institute grant P30 CA177558, USA ). We also thank the Imaging Core Facility of the COBRE ( P20 GM121327, USA ) for providing the imaging systems. This study was supported by grants from the National Institute of Health (NIH), USA ( R01GM079684 and R35GM131807 ) to J. J.
Publisher Copyright:
© 2019 Elsevier Inc.
Keywords
- ATGL
- Bmm
- Ci
- Fat body
- Hh
- Lipid droplet
- Lipolysis
- Smo
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology