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Metabolic disease and ABHD6 alter the circulating bis(monoacylglycerol)phosphate profile in mice and humans.
Journal of Lipid Research 2019 March 21
Bis(monoacylglycerol)phosphate (BMP) is a phospholipid crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSD) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders other than LSD, however, are scarce and key enzymes regulating BMP metabolism remain elusive. Here, we demonstrate that common metabolic disorders and the intracellular BMP hydrolase alpha/beta hydrolase domain containing 6 (ABHD6) affect BMP metabolism in mice and humans. In mice, dietary lipid overload strongly affects BMP concentration and fatty acid composition in liver and plasma similar as observed in LSD. Notably, distinct changes in the BMP fatty acid profile enable a clear distinction between lipid overload and drug-induced LSD. Global deletion of ABHD6 increases circulating BMP concentrations but does not cause LSD. In humans, non-alcoholic fatty liver disease and liver cirrhosis affect the serum BMP fatty acid composition and concentration. Furthermore, we identified a patient with a loss-of-function mutation in the ABHD6 gene leading to an altered circulating BMP profile. In conclusion, our results suggest that common metabolic diseases and ABHD6 affect BMP metabolism in mice and humans.
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