Starvation-induced regulation of carbohydrate transport at the blood-brain barrier is TGF-β-signaling dependent

• Published in: eLife Vol. 10
• Main Authors: Hertenstein, Helen, McMullen, Ellen, Weiler, Astrid, Volkenhoff, Anne, Becker, Holger M, Schirmeier, Stefanie
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 25-05-2021; eLife Sciences Publications, Ltd
• Subjects: Alzheimer's disease; Animals; Biological Transport; Blood-Brain Barrier; Brain; Carbohydrate Metabolism; carbohydrate transport; Carbohydrates; Cell Biology; Chondrocytes; Drosophila; Gene Expression Regulation; Glucose; Glucose - metabolism; Glucose transporter; Hunger; Hypoglycemia; Insects; Insulin; Kinases; Malnutrition; Mammals; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Molecular modelling; Nervous system; Neuroglia - cytology; Neuroglia - metabolism; Nutrients; Plasma; Proteins; rab GTP-Binding Proteins - metabolism; Signal Transduction; Starvation; TGF-β signaling; Transcription; Transcription, Genetic; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Trehalose - metabolism; Up-Regulation; blood-brain barrier; cell biology; D. melanogaster; TGF-β signaling; carbohydrate transport
• DOI: 10.7554/eLife.62503
• EISSN: 2050-084X

During hunger or malnutrition, animals prioritize alimentation of the brain over other organs to ensure its function and, thus, their survival. This protection, also-called brain sparing, is described from
to humans. However, little is known about the molecular mechanisms adapting carbohydrate transport. Here, we used
genetics to unravel the mechanisms operating at the blood-brain barrier (BBB) under nutrient restriction. During starvation, expression of the carbohydrate transporter Tret1-1 is increased to provide more efficient carbohydrate uptake. Two mechanisms are responsible for this increase. Similar to the regulation of mammalian GLUT4, Rab-dependent intracellular shuttling is needed for Tret1-1 integration into the plasma membrane; even though Tret1-1 regulation is independent of insulin signaling. In addition, starvation induces transcriptional upregulation that is controlled by TGF-β signaling. Considering TGF-β-dependent regulation of the glucose transporter GLUT1 in murine chondrocytes, our study reveals an evolutionarily conserved regulatory paradigm adapting the expression of sugar transporters at the BBB.