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Dehydration promotes intracellular lipid synthesis and accumulation

Carty, J. S.; Selvasingh, J.; Zuchowski, Y.; Nam, H.-J.; Penalva, C.; Nanayakkara, G.; Jennings, E. Q.; Voss, K.; Adame, E. T.; Tossberg, J.; Yap, W. S.; Melzer, M.; Viquez, O.; McCall, A. S.; Piotrowski, E. R.; Bessho, R.; Cao, S.; Leaptrot, K.; Schrimpe-Rutledge, A. C.; Codreanu, S. G.; Sherrod, S. D.; McLean, J. A.; Trapani, J. B.; Cottam, M. A.; Wan, M.; Shrivastava, D.; Delker, D. A.; Wilson, M. H.; Hassenour, C. M.; Lantier, L.; Chernova, I.; Young, J. D.; Haase, V. H.; Medina, J.-P. V.; Kosma, D. K.; Kim, P.; Cartailler, J. P.; Zhang, M.; Zent, R.; Harris,, R. C.; Watts, J. A.; Terker,

2025-08-11 physiology
10.1101/2025.08.07.669190 bioRxiv
Show abstract

Lipids can be considered a water reservoir used to offset dehydration stress as their oxidation by the mitochondria generates water. However, whether dehydration and the ensuing hypertonic stress directly regulate lipid synthesis is unknown. We found that hypertonic stress decreases cellular oxygen consumption, increases intracellular lipid synthesis, and favors glutamine oxidation as a carbon precursor for lipid synthesis via remodeling mitochondrial metabolism. These findings provide a mechanism whereby cellular dehydration leads to intracellular lipid accumulation, functionally linking water availability to lipid storage.

Published in Nature Communications (predicted rank #5) · training set

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