4.8 Article

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

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ELIFE
Volume 10, Issue -, Pages -

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ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.62503

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  1. Deutsche Forschungsgemeinschaft [SFB1009, SCHI 1380/2-1]

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During hunger or malnutrition, animals prioritize ensuring the supply of nutrients to the brain for survival, a mechanism known as brain sparing. Research in Drosophila has shown that the expression of carbohydrate transporter proteins increases during starvation to facilitate efficient carbohydrate uptake, regulated by Rab-dependent intracellular shuttling and TGF-beta signaling. This study reveals an evolutionarily conserved regulatory paradigm for sugar transporter expression at the blood-brain barrier.
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 Drosophila to humans. However, little is known about the molecular mechanisms adapting carbohydrate transport. Here, we used Drosophila 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-beta signaling. Considering TGF-beta-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.

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