Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis

Madalina Duta-Mare, Vinay Sachdev, Christina Leopold, Dagmar Kolb, Nemanja Vujic, Melanie Korbelius, Dina C. Hofer, Wenmin Xia, Katharina Huber, Martina Auer, Benjamin Gottschalk, Christoph Magnes, Wolfgang F. Graier, Andreas Prokesch, Branislav Radovic, Juliane G. Bogner-Strauss, Dagmar Kratky

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

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.

Originalspracheenglisch
Seiten (von - bis)467-478
Seitenumfang12
FachzeitschriftBiochimica et Biophysica Acta / Molecular and Cell Biology of Lipids
Jahrgang1863
Ausgabenummer4
DOIs
PublikationsstatusVeröffentlicht - 1 Apr 2018

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Sterol Esterase
Brown Adipose Tissue
Thermogenesis
Fatty Acids
Lysosomes
Lipids
Lipoprotein Lipase
Cholesterol Esters
Dyslipidemias
Hypothermia
Lipoproteins
Triglycerides
Hydrolysis
Messenger RNA
Temperature
Enzymes

Schlagwörter

    ASJC Scopus subject areas

    • !!Molecular Biology
    • Zellbiologie

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    Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis. / Duta-Mare, Madalina; Sachdev, Vinay; Leopold, Christina; Kolb, Dagmar; Vujic, Nemanja; Korbelius, Melanie; Hofer, Dina C.; Xia, Wenmin; Huber, Katharina; Auer, Martina; Gottschalk, Benjamin; Magnes, Christoph; Graier, Wolfgang F.; Prokesch, Andreas; Radovic, Branislav; Bogner-Strauss, Juliane G.; Kratky, Dagmar.

    in: Biochimica et Biophysica Acta / Molecular and Cell Biology of Lipids, Jahrgang 1863, Nr. 4, 01.04.2018, S. 467-478.

    Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

    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 2018, 'Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis' Biochimica et Biophysica Acta / Molecular and Cell Biology of Lipids, Jg. 1863, Nr. 4, S. 467-478. https://doi.org/10.1016/j.bbalip.2018.01.011
    Duta-Mare, Madalina ; Sachdev, Vinay ; Leopold, Christina ; Kolb, Dagmar ; Vujic, Nemanja ; Korbelius, Melanie ; Hofer, Dina C. ; Xia, Wenmin ; Huber, Katharina ; Auer, Martina ; Gottschalk, Benjamin ; Magnes, Christoph ; Graier, Wolfgang F. ; Prokesch, Andreas ; Radovic, Branislav ; Bogner-Strauss, Juliane G. ; Kratky, Dagmar. / Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis. in: Biochimica et Biophysica Acta / Molecular and Cell Biology of Lipids. 2018 ; Jahrgang 1863, Nr. 4. S. 467-478.
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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.",
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    AU - Duta-Mare, Madalina

    AU - Sachdev, Vinay

    AU - Leopold, Christina

    AU - Kolb, Dagmar

    AU - Vujic, Nemanja

    AU - Korbelius, Melanie

    AU - Hofer, Dina C.

    AU - Xia, Wenmin

    AU - Huber, Katharina

    AU - Auer, Martina

    AU - Gottschalk, Benjamin

    AU - Magnes, Christoph

    AU - Graier, Wolfgang F.

    AU - Prokesch, Andreas

    AU - Radovic, Branislav

    AU - Bogner-Strauss, Juliane G.

    AU - Kratky, Dagmar

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