Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Akhmetshina, A; Schooltink, L; Amor, M; Kuentzel, KB; Rainer, S; Nandy, A; Habisch, H; Madl, T; Rendina-Ruedy, E; Leithner, K; Vujić, N; Kratky, D.
Loss or inhibition of lysosomal acid lipase in vitro leads to cholesteryl ester accumulation without affecting muscle formation or mitochondrial function.
BBA Adv. 2025; 7: 100135
Doi: 10.1016/j.bbadva.2024.100135
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- Führende Autor*innen der Med Uni Graz
- Akhmetshina Alena
- Kratky Dagmar
- Co-Autor*innen der Med Uni Graz
- Amor Melina
- Habisch Hansjörg
- Küntzel Katharina Barbara
- Leithner Katharina
- Madl Tobias
- Rainer Silvia
- Schooltink Laszlo
- Vujic Nemanja
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- Abstract:
- Skeletal muscle (SM) is essential for movement, stability, and overall body function, and it readily adapts to changes in energy demand. Myogenesis is energy-intensive and involves complex molecular and cellular events. We recently demonstrated that the absence of lysosomal acid lipase (LAL) in vivo significantly impacts the SM phenotype, primarily by disrupting energy homeostasis and reducing ATP production. As systemic LAL deficiency affects multiple organs, we hypothesized that the altered SM phenotype resulted from systemic rather than SM-specific loss of LAL activity. To distinguish between systemic and cell-intrinsic effects, we used primary myoblasts isolated from Lal-deficient (-/-) mice as well as C2C12 cells treated with the pharmacological inhibitor of LAL, Lalistat-2. We found a significant accumulation of cholesteryl esters in both models studied, highlighting the central role of LAL in lipid catabolism in the SM. However, lipid accumulation was absent under lipoprotein-deficient culture conditions. Neither genetic loss nor pharmacological inhibition of LAL affected myofiber formation or mitochondrial function in vitro, in contrast to what we observed in SM isolated from Lal-/- mice. Tracing [13C6]-labeled glucose in both cell culture models revealed only minor changes in tricarboxylic acid cycle metabolites. These results suggest that although LAL plays an essential role in lipid metabolism, its impact on the processes involved in muscle differentiation and cellular energy production is minor. We conclude that the cell-intrinsic effects of Lal-/- SM are unlikely to drive the SM phenotype observed in vivo.
- Find related publications in this database (Keywords)
- LAL
- LAL deficiency
- Energy metabolism
- Primary myoblast
- Skeletal muscle
- Myogenesis