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SHR Neuro Krebs Kardio Lipid

Leopold, C; Duta-Mare, M; Sachdev, V; Goeritzer, M; Maresch, LK; Kolb, D; Reicher, H; Wagner, B; Stojakovic, T; Ruelicke, T; Haemmerle, G; Hoefler, G; Sattler, W; Kratky, D.
Hepatocyte-specific lysosomal acid lipase deficiency protects mice from diet-induced obesity but promotes hepatic inflammation.
Biochim Biophys Acta Mol Cell Biol Lipids. 2019; 1864(4):500-511 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Duta-Mare Madalina-Cristina
Göritzer Madeleine
Hoefler Gerald
Kolb Dagmar
Kratky Dagmar
Leopold Christina
Reicher Helga
Sachdev Vinay
Sattler Wolfgang
Stojakovic Tatjana
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Abstract:
Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CE) and triglycerides (TG) to generate fatty acids (FA) and cholesterol. LAL deficiency (LAL-D) in both humans and mice leads to hepatomegaly, hypercholesterolemia, and shortened life span. Despite its essential role in lysosomal neutral lipid catabolism, the cell type-specific contribution of LAL to disease progression is still elusive. To investigate the role of LAL in the liver in more detail and to exclude the contribution of LAL in macrophages, we generated hepatocyte-specific LAL-deficient mice (Liv-Lipa-/-) and fed them either chow or high fat/high cholesterol diets (HF/HCD). Comparable to systemic LAL-D, Liv-Lipa-/- mice were resistant to diet-induced obesity independent of food intake, movement, and energy expenditure. Reduced body weight gain was mainly due to reduced white adipose tissue depots. Furthermore, Liv-Lipa-/- mice exhibited improved glucose clearance during glucose and insulin tolerance tests compared to control mice. Analysis of hepatic lipid content revealed a massive reduction of TG, whereas CE concentrations were markedly increased, leading to CE crystal formation in the livers of Liv-Lipa-/- mice. Elevated plasma transaminase activities, increased pro-inflammatory cytokines and chemokines as well as hepatic macrophage infiltration indicated liver inflammation. Our data provide evidence that hepatocyte-specific LAL deficiency is sufficient to alter whole-body lipid and energy homeostasis in mice. We conclude that hepatic LAL plays a pivotal role by preventing liver damage and maintaining lipid and energy homeostasis, especially during high lipid availability. Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.

Find related publications in this database (Keywords)
LAL-D
Cholesteryl ester storage disease
Wolman disease
Fibrosis
Liver damage
Lipid
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