Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid Metabolism in

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Liver kinase B1 (LKB1), a serine/threonine kinase, controls 14 different AMP-activated protein kinase (AMPK) family kinases, including salt-inducible kinase 3 (SIK3), suggesting that it plays a variety of roles. Using the fruit fly as an in vivo model system, we reveal that LKB1 kinase activity is critical for lipid storage and controls the lipolysis pathway in the fat body, which is equivalent to mammalian adipose and liver tissue. We find that the lipolytic defects of LKB1 mutants are rescued by the expression of constitutively active SIK3 in the fat body. We show that LKB1 and SIK3 regulate lipid storage by altering the gene expression of brummer, the Drosophila homolog of human adipose triglyceride lipase (ATGL), a critical lipolytic gene. We also identify that LKB1-SIK3 signaling controls the nuclear and cytosolic localization of the class IIa deacetylase HDAC4 via SIK3-dependent phosphorylation in feeding and fasting conditions, respectively. Collectively, these data suggest that the LKB1-SIK3-HDAC4 pathway plays a critical role in maintaining fly lipid homeostasis in response to dietary conditions.

Vyšlo v časopise: Feeding and Fasting Signals Converge on the LKB1-SIK3 Pathway to Regulate Lipid Metabolism in. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005263
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005263

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