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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Kuentzel, KB; Bradić, I; Akhmetshina, A; Korbelius, M; Rainer, S; Kolb, D; Gauster, M; Vujić, N; Kratky, D.
Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth.
Int J Mol Sci. 2021; 22(19): Doi: 10.3390/ijms221910416 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Kratky Dagmar
Küntzel Katharina Barbara
Co-Autor*innen der Med Uni Graz
Akhmetshina Alena
Bradic Ivan
Gauster Martin
Kolb Dagmar
Korbelius Melanie
Rainer Silvia
Vujic Nemanja

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Cholesterol and fatty acids are essential lipids that are critical for membrane biosynthesis and fetal organ development. Cholesteryl esters (CE) are degraded by hormone-sensitive lipase (HSL) in the cytosol and by lysosomal acid lipase (LAL) in the lysosome. Impaired LAL or HSL activity causes rare pathologies in humans, with HSL deficiency presenting less severe clinical manifestations. The infantile form of LAL deficiency, a lysosomal lipid storage disorder, leads to premature death. However, the importance of defective lysosomal CE degradation and its consequences during early life are incompletely understood. We therefore investigated how defective CE catabolism affects fetus and infant maturation using Lal and Hsl knockout (-/-) mouse models. This study demonstrates that defective lysosomal but not neutral lipolysis alters placental and fetal cholesterol homeostasis and exhibits an initial disease pathology already in utero as Lal-/- fetuses accumulate hepatic lysosomal lipids. Immediately after birth, LAL deficiency exacerbates with massive hepatic lysosomal lipid accumulation, which continues to worsen into young adulthood. Our data highlight the crucial role of LAL during early development, with the first weeks after birth being critical for aggravating LAL deficiency.

Find related publications in this database (Keywords)
cholesterol catabolism
lysosomal acid lipase
lysosomal storage disorder
mutant mouse models
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