Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1863, Issue 4, Pages 467-478Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2018.01.011
Keywords
Brown adipose tissue; LAL deficiency; Lysosome; UCP1; Thermogenesis; Dyslipidemia
Funding
- Austrian Science Fund FWF [DKMCD W1226, P27070, P27108, P29328, 13165, SFB-LIPOTOX F30]
- BioTechMed-Graz
- Medical University of Graz
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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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