A5038116384- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Ubiquitin and proteasome pathways
- Neurobiology and Insect Physiology Research
- Nuclear Structure and Function
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Neuroblastoma Research and Treatments
- Advanced Proteomics Techniques and Applications
- Hydrocarbon exploration and reservoir analysis
- Bioinformatics and Genomic Networks
- Lipid metabolism and biosynthesis
- NF-κB Signaling Pathways
- Muscle metabolism and nutrition
- Protein Kinase Regulation and GTPase Signaling
- Physiological and biochemical adaptations
- Cell death mechanisms and regulation
- Reservoir Engineering and Simulation Methods
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- Hydraulic Fracturing and Reservoir Analysis
Wellcome/MRC Institute of Metabolic Science
2022-2023
University of Cambridge
2022-2023
Wellcome Trust
2023
The University of Sydney
2018-2023
Medical Research Council
2022
Abstract The failure of metabolic tissues to appropriately respond insulin (“insulin resistance”) is an early marker in the pathogenesis type 2 diabetes. Protein phosphorylation central adipocyte response, but how signaling networks are dysregulated upon resistance unknown. Here we employ phosphoproteomics delineate signal transduction cells and adipose tissue. Across a range insults causing resistance, observe marked rewiring network. This includes both attenuated insulin-responsive...
Adipose tissue is essential for whole-body glucose homeostasis, with a primary role in lipid storage. It has been previously observed that lactate production also an important metabolic feature of adipocytes, but its relationship to adipose and disposal remains unclear. Therefore, using combination labeling techniques, here we closely examined cultured mammalian adipocytes. Insulin treatment increased uptake conversion lactate, the latter responding more insulin than did other fates glucose....
Exercise engages signaling networks to control the release of circulating factors beneficial health. However, nature these remains undefined. Using high-throughput phosphoproteomics, we quantify 20,249 phosphorylation sites in skeletal muscle-like myotube cells and monitor their responses a panel cell stressors targeting aspects exercise vivo. Integrating in-depth phosphoproteomes with phosphoproteome acute aerobic human muscle suggests that co-administration β-adrenergic calcium agonists...
Central to the development of heart failure with preserved ejection fraction (HFpEF) is redox disruption metabolic processes, however, underlying mechanisms are not fully understood. This study utilized a murine model (ND6) carrying homoplasmic mitochondrial DNA point mutation ( ND6 G13997A), which maintains functional NADH oxidation but lacks site-specific reactive oxygen species (ROS) generation via reverse electron transport (RET). We demonstrate that mice RET-ROS deficiency have reduced...
Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to a PI3K/Akt-dependent manner novel substrate for GSK3. Priming phosphorylation murine at serine 84 allows GSK3-directed serines 72, 76 80. A similar pattern was observed human suggesting our findings are...
Abstract The failure of metabolic tissues to appropriately respond insulin (“insulin resistance”) is an early marker in the pathogenesis type 2 diabetes. Protein phosphorylation central adipocyte response, but how signaling networks are dysregulated upon resistance unknown. Here we employed phosphoproteomics delineate signal transduction cells and adipose tissue. Across a range insults triggering resistance, observed marked rewiring network. This included both attenuated insulin-responsive...
Insulin-induced GLUT4 translocation to the plasma membrane in muscle and adipocytes is crucial for whole-body glucose homeostasis. Currently, trafficking assays rely on overexpression of tagged GLUT4. Here we describe a high-content imaging platform studying endogenous intact adipocytes. This method enables high fidelity analysis responses specific perturbations, multiplexing other proteins features including lipid droplet morphology. Using this multiplexed approach showed that Vps45 Rab14...
Mitochondrial dysfunction has been reported in obesity and insulin resistance, but primary genetic mitochondrial is generally not associated with these, arguing against a straightforward causal relationship. A rare exception, recently identified humans, syndrome of lower body adipose loss, leptin-deficient severe upper overgrowth, resistance caused by the p.Arg707Trp mutation MFN2 , encoding mitofusin 2. How resulting selective form leads to tissue- depot-specific growth abnormalities...
Trafficking regulator of GLUT4 1 (TRARG1) was recently identified to localize glucose transporter type 4 (GLUT4) storage vesicles (GSVs) and positively regulate trafficking. Our knowledge TRARG1 structure membrane topology is limited predictive models, hampering efforts further our mechanistic understanding how it carries out its functions. Here, we use a combination bioinformatics prediction tools biochemical assays define the 173-amino acid mouse TRARG1. These analyses revealed that,...
Abstract Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to a PI3K/Akt-dependent manner novel substrate for GSK3. Priming phosphorylation murine at serine 84 allows GSK3-directed serines 72, 76 80. A similar pattern was observed human suggesting our...