New Imaging Technique Reveals How Cells Organize Glucose Processing

In a technological first, researchers from Vanderbilt University and nan University of California, San Diego, person generated a high-resolution metabolic "map" of really cells orchestrate glucose processing, revealing a hidden world wherever organelles and molecular complexes collaborate erstwhile responding to a unreserved of nutrients. This caller study, published in Nature Communications, has redefined really glucose metabolism is visualized astatine nan single-cell level. The pioneering activity provides some a caller method and insights into an organizational and molecular model that tin beryllium utilized to study really metabolic processes are disrupted successful diseases for illustration diabetes, obesity, and cancer, arsenic good arsenic successful aging and neurodegeneration.

"This is simply a caller field-we are astatine nan forefront by integrating aggregate microscopy modes into blase pipelines to measurement nan destiny of glucose atoms, from full animals to organelles, and to show nan underlying subcellular architecture associated pinch these processes successful cells," Rafael Arrojo e Drigo said. Arrojo e Drigo is an adjunct professor of molecular physiology and biophysics and nan corresponding writer of nan study. "We expect that this beforehand will propel a caller programme that exploits these precocious investigational strategies to study and amended understand really nutrient metabolism is organized wrong nan highly system domains of cells and tissues, which allows for nan precise regularisation of organ usability successful nan discourse of whole-animal physiology."

To date, what scientists cognize astir really cells process nutrients for illustration glucose has been derived from bulk metabolomics. Using metabolomics, researchers tin analyse an full group of mini molecules wrong a biologic sample, specified arsenic a tissue, but it's done without information of nan circumstantial spatial aliases subcellular contexts successful which they occur.

These bulk strategies do not uncover nan spatial characteristics of compartment metabolism astatine nan single-cell level aliases really these aspects subordinate to nan location of cells and organelles wrong nan complexity of nan insubstantial they reside within."

Rafael Arrojo e Drigo, assistant professor of molecular physiology and biophysics and corresponding writer of nan study

This spread successful nan field's knowing drove a multidisciplinary squad from Vanderbilt, nan Vanderbilt University Medical Center, and UCSD to harvester unchangeable isotope tracing, multi-scale microscopy, and AI-powered image study to representation glucose metabolites astatine animal, tissue, cellular, and organellar scales. The Vanderbilt squad was led by co-first authors Christopher Acree and Aliyah Habashy from the Arrojo e Drigo lab and included scientists from the Vanderbilt Mouse Metabolic Phenotyping Center, the Mass Spectrometry Research Center, the Department of Cell and Developmental Biology, and nan VUMC Department of Surgery. Researchers from Mark Ellisman's group astatine nan National Center for Microscopy and Imaging Research astatine UCSD rounded retired nan collaboration.

Together, they wished nan spatial statement of glucose metabolites, from wrong full animals to wrong liver cells and moreover successful individual mitochondria. Using isotopically branded glucose infusions successful unrecorded mice, nan researchers mapped really glucose-derived carbons were incorporated into glycogen, lipid droplets, and different cellular components complete time.

Among nan awesome discoveries of this study, nan squad uncovered a antecedently unrecognized structural and functional relationship betwixt lipid droplets and glycogen synthesis. In addition, nan researchers mapped really contacts betwixt mitochondria and nan endoplasmic reticulum-two cardinal organelles progressive successful power accumulation and nutrient sensing-shift dynamically successful consequence to changes successful humor glucose levels. These mitochondria-ER contacts shape portion of a broader organelle web that coordinates metabolic responses wrong nan cell. By charting nan timeline of these interactions, nan study offers caller insights into really organelles reorganize to accommodate to different metabolic states, shedding ray connected basal mechanisms of glucose metabolism and cellular power balance.

This breakthrough was made imaginable by Vanderbilt's characteristic interdisciplinary situation and nan multi-scale, multi-modal imaging thrust of nan NCMIR, an confederation that brought together experts successful unchangeable isotope tracing, successful vivo animal metabolism, wide spectrometry imaging, AI, and computational modeling, Arrojo e Drigo said. Looking ahead, nan squad hopes to understand really nan spatial statement of nutrients wrong cells contributes to metabolic wellness and disease.