Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis.
Biochim Biophys Acta Mol Cell Biol Lipids
; 1863(4): 467-478, 2018 Apr.
Article
em En
| MEDLINE
| ID: mdl-29374543
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo Marrom
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Esterol Esterase
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Termogênese
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Ácidos Graxos
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Biol Lipids
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Áustria