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Baldini, Giulia
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overview
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• Obesity is a major risk factor in the development of the metabolic syndrome, which is characterized by hypertension, glucose intolerance, insulin resistance, dyslipidemia, and increased propensity to develop diabetes type 2.
• A likely cofactor promoting the alarming increase in obesity in the last 10 years is the availability of food with high caloric and fat content. Exposure to a hypercaloric, high-fat diet induces lipid stress in regions of the hypothalamus controlling appetite.
• Melanocortin-4 Receptor (MC4R), a G-protein coupled receptor (GPCR) expressed by neurons of the hypothalamus controls appetite and is thereby considered a relevant target for anti-obesity therapies. However, even very potent MC4R agonists do not appear to treat obesity in mice and humans. The underlying mechanisms by which such agonists are ineffective are yet unclear.
• Our research aims to discover how lipid stress, such as that induced by high fat diet, affects MC4R abundance, signaling, and intracellular traffic; whether chemical chaperones can rescue function of MC4R in lipid stressed neurons; and whether different synthetic MC4R agonists have specific effects to promote MC4R signaling.
• Our research analyzes MC4R function in cultured hypothalamic neurons, neuronal cells, and the murine hypothalamus by using state-of-the-art techniques, such as Quantitative Fluorescence Microscopy, including Förster Resonance Energy Transfer and Fluorescence Recovery After Photobleaching, Super-Resolution Microscopy, Electron Microscopy and Mass Spectrometry.
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Baldini, Giulia