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SHR Neuro Krebs Kardio Lipid

Duta-Mare, M; Sachdev, V; Leopold, C; Kolb, D; Vujic, N; Korbelius, M; Hofer, DC; Xia, W; Huber, K; Auer, M; Gottschalk, B; Magnes, C; Graier, WF; Prokesch, A; Radovic, B; Bogner-Strauss, JG; Kratky, D.
Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis.
Biochim Biophys Acta. 2018; 1863(4):467-478 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Auer Martina
Duta-Mare Madalina-Cristina
Gottschalk Benjamin
Graier Wolfgang
Kolb-Lenz Dagmar
Korbelius Melanie
Kratky Dagmar
Leopold Christina
Prokesch Andreas
Radovic Branislav
Sachdev Vinay
Vujic Nemanja
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Abstract:
Lysosomal acid lipase (LAL) is the only known enzyme, which hydrolyzes cholesteryl esters and triacylglycerols in lysosomes of multiple cells and tissues. Here, we explored the role of LAL in brown adipose tissue (BAT). LAL-deficient (Lal-/-) mice exhibit markedly reduced UCP1 expression in BAT, modified BAT morphology with accumulation of lysosomes, and mitochondrial dysfunction, consequently leading to regular hypothermic events in mice kept at room temperature. Cold exposure resulted in reduced lipid uptake into BAT, thereby aggravating dyslipidemia and causing life threatening hypothermia in Lal-/- mice. Linking LAL as a potential regulator of lipoprotein lipase activity, we found Angptl4 mRNA expression upregulated in BAT. Our data demonstrate that LAL is critical for shuttling fatty acids derived from circulating lipoproteins to BAT during cold exposure. We conclude that inhibited lysosomal lipid hydrolysis in BAT leads to impaired thermogenesis in Lal-/- mice. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Find related publications in this database (Keywords)
Brown adipose tissue
LAL deficiency
Lysosome
UCP1
Thermogenesis
Dyslipidemia
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