ArticlePLoS genetics2015
Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid Metabolism in Drosophila.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 92 citations in OpenAlex.
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- Transcriptional Control of Lipid Metabolism.Advances in experimental medicine and biology · 2026Review
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- SIK2 and SIK3 Differentially Regulate Mouse Granulosa Cell Response to Exogenous Gonadotropins In Vivo.Endocrinology · 2024Article
- Rapid response of fly populations to gene dosage across development and generations.Nature communications · 2024Article
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- Adipokinetic hormone signaling in the malaria vector Anopheles gambiae facilitates Plasmodium falciparum sporogony.Communications biology · 2023Article
- Of Mice and Men and Plethysmography Systems: Does LKB1 Determine the Set Point of Carotid Body Chemosensitivity and the Hypoxic Ventilatory Response?Advances in experimental medicine and biology · 2023Article
- A phosphorylation-deficient mutant ofFrontiers in neuroscience · 2023Article
- The role of liver kinase B1 in tumor progression through regulation of lipid metabolism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- LKB1 is physiologically required for sleep from Drosophila melanogaster to the Mus musculus.Genetics · 2022Article
- LKB1 is the gatekeeper of carotid body chemosensing and the hypoxic ventilatory response.Communications biology · 2022Article
- Salt-inducible kinase 3 protects tumor cells from cytotoxic T-cell attack by promoting TNF-induced NF-κB activation.Journal for immunotherapy of cancer · 2022Article
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- Nutrient Sensing via Gut inInternational journal of molecular sciences · 2022Review
- Sex determination geneeLife · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LKB1 plays important roles in governing energy homeostasis by regulating AMP-activated protein kinase (AMPK) and other AMPK-related kinases, including the salt-inducible kinases (SIKs). However, the roles and regulation of LKB1 in lipid metabolism are poorly understood. Here we show that Drosophila LKB1 mutants display decreased lipid storage and increased gene expression of brummer, the Drosophila homolog of adipose triglyceride lipase (ATGL). These phenotypes are consistent with those of SIK3 mutants and are rescued by expression of constitutively active SIK3 in the fat body, suggesting that SIK3 is a key downstream kinase of LKB1. Using genetic and biochemical analyses, we identify HDAC4, a class IIa histone deacetylase, as a lipolytic target of the LKB1-SIK3 pathway. Interestingly, we found that the LKB1-SIK3-HDAC4 signaling axis is modulated by dietary conditions. In short-term fasting, the adipokinetic hormone (AKH) pathway, related to the mammalian glucagon pathway, inhibits the kinase activity of LKB1 as shown by decreased SIK3 Thr196 phosphorylation, and consequently induces HDAC4 nuclear localization and brummer gene expression. However, under prolonged fasting conditions, AKH-independent signaling decreases the activity of the LKB1-SIK3 pathway to induce lipolytic responses. We also identify that the Drosophila insulin-like peptides (DILPs) pathway, related to mammalian insulin pathway, regulates SIK3 activity in feeding conditions independently of increasing LKB1 kinase activity. Overall, these data suggest that fasting stimuli specifically control the kinase activity of LKB1 and establish the LKB1-SIK3 pathway as a converging point between feeding and fasting signals to control lipid homeostasis in Drosophila.
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