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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)467-478
Number of pages12
JournalBiochimica et Biophysica Acta / Molecular and Cell Biology of Lipids
Volume1863
Issue number4
DOIs
Publication statusPublished - 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

Keywords

  • Brown adipose tissue
  • Dyslipidemia
  • LAL deficiency
  • Lysosome
  • Thermogenesis
  • UCP1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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, Vol. 1863, No. 4, 01.04.2018, p. 467-478.

Research output: Contribution to journalArticleResearchpeer-review

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, vol. 1863, no. 4, pp. 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 ; Vol. 1863, No. 4. pp. 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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