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

被引：28

作者：

Duta-Mare, Madalina ^{[1
]}

Sachdev, Vinay ^{[1
]}

Leopold, Christina ^{[1
]}

Kolb, Dagmar ^{[1
,2
]}

Vujic, Nemanja ^{[1
]}

Korbelius, Melanie ^{[1
]}

Hofer, Dina C. ^{[3
]}

Xia, Wenmin ^{[3
]}

Huber, Katharina ^{[3
]}

Auer, Martina ^{[1
]}

Gottschalk, Benjamin ^{[1
]}

Magnes, Christoph ^{[4
]}

Graier, Wolfgang F. ^{[1
,5
]}

Prokesch, Andreas ^{[1
]}

Radovic, Branislav ^{[1
,5
]}

Bogner-Strauss, Juliane G. ^{[3
,5
]}

Kratky, Dagmar ^{[1
,5
]}

机构：

[1] Med Univ Graz, Gottfried Schatz Res Ctr, Neue Stiftingtalstr 6-6, A-8010 Graz, Austria

[2] Med Univ Graz, Ctr Med Res, Graz, Austria

[3] Graz Univ Technol, Inst Biochem, Graz, Austria

[4] Joanneum Res, Hlth Bioanalyt & Metabol, Graz, Austria

[5] BioTechMed Graz, Graz, Austria

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2018年 / 1863卷 / 04期

基金：

奥地利科学基金会;

关键词：

Brown adipose tissue; LAL deficiency; Lysosome; UCP1; Thermogenesis; Dyslipidemia; ESTER STORAGE-DISEASE; ADAPTIVE NONSHIVERING THERMOGENESIS; CHOLESTERYL ESTER; TARGETED DISRUPTION; INSULIN SENSITIVITY; TRIGLYCERIDE LIPASE; METABOLISM; LIPOLYSIS; ADIPOCYTES; LIVER;

D O I：

10.1016/j.bbalip.2018.01.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：467 / 478

页数：12

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