Hepatic lysosomal acid lipase drives the autophagy-lysosomal response and alleviates cholesterol metabolic disorder in ApoE deficient mice

Li, Feifei; Zhao, Xiaojie; Li, Hao; Liu, Yu; Zhang, Yu; Huang, Xiaopeng; Cao, Jia; Du, Fu‐Sheng; Wu, Dongcheng; Yu, Hong

doi:10.1016/j.bbalip.2021.159027

Cited by 3 publications

(1 citation statement)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sebelipase alfa has not yet been tested for NAFLD, CAD, or any indication other than LALD. Hepatic overexpression of LAL using lentivirus in a mouse model of NAFLD led to reduced steatosis and fibrosis, decreased liver inflammation, and decreased serum lipid levels ( Li et al, 2021 ); however, overexpression with an adeno-associated virus in a different mouse model of NAFLD did not attenuate steatosis, and increased liver inflammation ( Lopresti et al, 2021 ). Both studies showed increased autophagic activity in hepatocytes.…”

Section: The Role Of Lal In Fatty Liver Diseasementioning

confidence: 99%

Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease

Besler

Blanchard

2022

Front. Genet.

View full text Add to dashboard Cite

Lysosomal acid lipase (LAL), encoded by the gene LIPA, is the sole neutral lipid hydrolase in lysosomes, responsible for cleavage of cholesteryl esters and triglycerides into their component parts. Inherited forms of complete (Wolman Disease, WD) or partial LAL deficiency (cholesteryl ester storage disease, CESD) are fortunately rare. Recently, LAL has been identified as a cardiovascular risk gene in genome-wide association studies, though the directionality of risk conferred remains controversial. It has also been proposed that the low expression and activity of LAL in arterial smooth muscle cells (SMCs) that occurs inherently in nature is a likely determinant of the propensity of SMCs to form the majority of foam cells in atherosclerotic plaque. LAL also likely plays a potential role in fatty liver disease. This review highlights the nature of LAL gene mutations in WD and CESD, the association of LAL with prediction of cardiovascular risk from genome-wide association studies, the importance of relative LAL deficiency in SMC foam cells, and the need to further interrogate the pathophysiological impact and cell type-specific role of enhancing LAL activity as a novel treatment strategy to reduce the development and induce the regression of ischemic cardiovascular disease and fatty liver.

show abstract

Section: The Role Of Lal In Fatty Liver Diseasementioning

confidence: 99%

Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease

Besler

Blanchard

2022

Front. Genet.

View full text Add to dashboard Cite

show abstract

Recent insights into lysosomal acid lipase deficiency

Korbelius

Kuentzel

et al. 2023

Trends in Molecular Medicine

View full text Add to dashboard Cite

Lipophagy: A Potential Therapeutic Target for Diabetic Nephropathy

Yang

Song

Zhao

et al. 2023

CMC

View full text Add to dashboard Cite

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and one of the main causes of end-stage renal disease (ESRD). There are many factors causing the progression of DN. Lipid metabolism disorder is a common clinical manifestation of DN, and ectopic renal lipid deposition was recently proposed as a key factor promoting the development of DN. Lipophagy is a newly discovered type of selective autophagy, that can remove excessive lipids in cells in time to maintain lipid homeostasis in cells. Recently, abnormalities in lipophagy have also been implicated in the progression of DN. Here, we discuss the formation of lipid droplets, describe lipophagy and its key regulatory signals, summarize the current research progress of lipophay in DN, and finally propose on lipophagy may be a potential target for the treatment of DN.

show abstract

Hepatic lysosomal acid lipase drives the autophagy-lysosomal response and alleviates cholesterol metabolic disorder in ApoE deficient mice

Cited by 3 publications

References 40 publications

Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease

Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease

Recent insights into lysosomal acid lipase deficiency

Lipophagy: A Potential Therapeutic Target for Diabetic Nephropathy

Contact Info

Product

Resources

About