Chronic stress, modeled by flattened circadian glucocorticoid (GC) oscillations, is increasingly implicated in obesity. We investigated the underlying mechanisms disrupting GC rhythms mice, elevating normally low levels during rest period. This disruption induced substantial obesity, comparable to a 60% high-fat diet (HFD), with additive effects on fat mass, suggesting distinct driving adiposity. Despite similar adiposity, GC-flattening and HFD produced profoundly different metabolic...

Highlights•Drosophila PIP4K mutant larvae have increased PIP3 levels in cells•Cells show enhanced sensitivity to insulin the absence of PIP4K•PIP4K regulates enzymes involved turnover at plasma membrane•Loss suppresses resistance phenotypesSummaryPhosphatidylinositol 3,4,5-trisphosphate (PIP3) generation membrane is a key event during activation receptor tyrosine kinases such as required for normal growth and metabolism. We report that Drosophila, phosphatidylinositol 5 phosphate 4-kinase...

Endocytic turnover is essential for the regulation of protein composition and function plasma membrane, thus affects membrane levels many receptors. In Drosophila melanogaster photoreceptors, photon absorption by G-protein-coupled receptor (GPCR) rhodopsin 1 (Rh1; also known as NinaE) triggers its endocytosis through clathrin-mediated (CME). We find that CME Rh1 regulated phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Flies lacking PIP4K show mislocalization on expanded endomembranes...

Phosphatidylinositol-5-phosphate (PI5P) is a low abundance lipid proposed to have functions in cell migration, DNA damage responses, receptor trafficking and insulin signalling metazoans. However, studies of PI5P function are limited by the lack scalable techniques quantify its level from cells tissues multicellular organisms. Currently, measurement requires use radionuclide labelling approaches that not easily applicable or vivo samples. In present study, we describe simple reliable,...

Abstract Lowe syndrome (LS) is an X-linked recessive genetic disorder characterized by renal dysfunction, neurodevelopmental defects, and cataract. The affected gene, OCRL encodes for a polyphosphoinositide 5-phosphatase. localized to multiple sub-cellular locations in the endolysosomal system defects these organelles have been described human cells depleted of OCRL. However, relationship altered physiology kidney LS patients has not completely determined. Here we model phenotypes using...

Phosphatidylinositol 3-phosphate (PI3P) and phosphatidylinositol 5-phosphate (PI5P) are low-abundance phosphoinositides crucial for key cellular events such as endosomal trafficking autophagy. 4-kinase (PIP4K) is an enzyme that regulates PI5P in vivo but can act on both PI3P vitro. In this study, we report a role PIP4K regulating levels Drosophila . Loss-of-function mutants of the only gene show reduced cell size salivary glands. elevated dPIP4K 29 reverting back towards WT, without changes...

How progenitor cells can attain a distinct differentiated cell identity is challenging problem given the fluctuating signaling environment in which exist and that critical transcription factors are often not unique to differentiation process. Here, we test hypothesis result from core component of state doubling up as protein also drives differentiation. Using live single-cell imaging adipocyte system, show fat (preadipocytes) only commit terminally differentiate after up-regulating FABP4,...

Human brain development is a complex process where multiple cellular and developmental events are coordinated to generate normal structure function. Alteration in any of these can impact development, manifesting clinically as neurodevelopmental disorders. genetic disorders lipid metabolism often present with features altered Lowe syndrome (LS) an X-linked recessive disease LS results from mutations OCRL1, which encodes phosphoinositide 5-phosphatase enzyme. However, the mechanisms by loss...

Phosphoinositides are lipid signaling molecules that regulate several conserved sub-cellular processes in eukaryotes, including cell growth. generated by the enzymatic activity of highly specific kinases and phosphatases. For example, PIP3, Class I PI3 kinase generates it phosphatase PTEN metabolizes all established regulators growth control metazoans. To identify additional functions for phosphoinositides control, we performed a genetic screen to proteins which when depleted result altered...

The ability to co-ordinate function between multiple cells is a critical requirement for multi-cellularity. This co-ordination mediated by hormones or growth factors, molecules secreted one cell type that can convey information the other and influence their behaviour. Hormone-dependent signalling second messenger systems;phosphoinositides (PIs) generated lipid kinase activity are such key system. Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) phosphorylates phosphatidylinositol...

The usefulness of spleen scans in the selection an area for further radiation therapy a refractory patient with chronic myeloid leukemia is demonstrated. Estimation degree reduction size response to treatment patients leukemia, Hodgkin's disease and polycythemia vera described as disappearance mass following endoxan therapy. value detecting presence or absence splenomegaly cases without palpable also discussed.

Abstract Phosphatidylinositol-3,4,5-trisphosphate (PIP 3 ) generation at the plasma membrane is a key event during activation of receptor tyrosine kinases such as insulin and critical for normal growth metabolism. The lipid phosphatases regulating PIP levels are described but mechanisms controlling their activity remain unclear. We report that in Drosophila , phosphatidylinositol 5 phosphate 4-kinase 4 K) function required activation. Depletion K increases augments sensitivity to through...

Abstract Phosphatidylinositol-5-phosphate (PI5P) is a low abundance lipid proposed to have functions in cell migration, DNA damage responses, receptor trafficking and insulin signalling metazoans. However, studies of PI5P function are limited by the lack scalable techniques quantify its level from cells tissues multicellular organisms. Currently, measurement requires use radionuclide labelling approaches that not easily applicable or vivo samples. In this study, we describe simple reliable,...

Abstract Phosphatidylinositol 3-phosphate (PI3P) and 5-phosphate (PI5P) are low abundant phosphoinositides crucial for key cellular events such as endosomal trafficking autophagy. 4-kinase (PIP4K) is an enzyme that regulates PI5P in vivo but can act on both PI3P, vitro . In this study, we report a novel role PIP4K regulating PI3P levels Drosophila tissues. Loss-of-function mutants of the only gene ( dPIP4K 29 ) show reduced cell size larval salivary glands. We find elevated tissues reverting...

Abstract Human brain development is a complex process where multiple cellular and developmental events are co-ordinated to generate normal structure function. Alteration in any of these can impact development, manifesting clinically as neurodevelopmental disorders. genetic disorders lipid metabolism often present with features altered Lowe syndrome (LS), X-linked recessive disease LS results from mutations OCRL1 that encodes phosphoinositide 5-phosphatase enzyme. However, the mechanisms by...