ArticleThe American journal of pathology2015
Hepatocyte-Specific Expression of Human Lysosome Acid Lipase Corrects Liver Inflammation and Tumor Metastasis in lal(-/-) Mice.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Secreted enzyme uptake masks the in vivo phenotype of macrophage-specific lysosomal acid lipase deletion.Molecular metabolism · 2026Article
- The role of lipophagy in liver cancer: mechanisms and targeted therapeutic interventions.Frontiers in cell and developmental biology · 2025Review
- Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives.Molecular cancer · 2024Review
- Emerging role of lipophagy in liver disorders.Molecular and cellular biochemistry · 2024Review
- Dissecting cell type-specific impact in lysosomal acid lipase deficiency-associated disorders.Journal of lipid research · 2023Article
- Sigma1 Regulates Lipid Droplet-mediated Redox Homeostasis Required for Prostate Cancer Proliferation.Cancer research communications · 2023Article
- Recent insights into lysosomal acid lipase deficiency.Trends in molecular medicine · 2023Review
- Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases.Biomedicines · 2023Review
- LAL deficiency induced myeloid-derived suppressor cells as targets and biomarkers for lung cancer.Journal for immunotherapy of cancer · 2023Article
- Lysosomal Acid Lipase Deficiency: Genetics, Screening, and Preclinical Study.International journal of molecular sciences · 2022Review
- Moderate Treadmill Exercise Alleviates NAFLD by Regulating the Biogenesis and Autophagy of Lipid Droplet.Nutrients · 2022Article
- Targeting the lysosome: Mechanisms and treatments for nonalcoholic fatty liver disease.Journal of cellular biochemistry · 2022Review
- 15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report.Medicine · 2022Article
- Autophagy and organelle homeostasis in cancer.Developmental cell · 2021Review
- Lysosomal Acid Lipase Deficiency Controls T- and B-Regulatory Cell Homeostasis in the Lymph Nodes of Mice with Human Cancer Xenotransplants.The American journal of pathology · 2021Article
- Review
- Biogenesis and Breakdown of Lipid Droplets in Pathological Conditions.Frontiers in cell and developmental biology · 2021Review
- Persistent dyslipidemia in treatment of lysosomal acid lipase deficiency.Orphanet journal of rare diseases · 2020Article
- The Double-Edge Sword of Autophagy in Cancer: From Tumor Suppression to Pro-tumor Activity.Frontiers in oncology · 2020Review
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The liver is a major organ for lipid synthesis and metabolism. Deficiency of lysosomal acid lipase (LAL; official name Lipa, encoded by Lipa) in mice (lal(-/-)) results in enlarged liver size due to neutral lipid storage in hepatocytes and Kupffer cells. To test the functional role of LAL in hepatocyte, hepatocyte-specific expression of human LAL (hLAL) in lal(-/-) mice was established by cross-breeding of liver-activated promoter (LAP)-driven tTA transgene and (tetO)7-CMV-hLAL transgene with lal(-/-) knockout (KO) (LAP-Tg/KO) triple mice. Hepatocyte-specific expression of hLAL in LAP-Tg/KO triple mice reduced the liver size to the normal level by decreasing lipid storage in both hepatocytes and Kupffer cells. hLAL expression reduced tumor-promoting myeloid-derived suppressive cells in the liver of lal(-/-) mice. As a result, B16 melanoma metastasis to the liver was almost completely blocked. Expression and secretion of multiple tumor-promoting cytokines or chemokines in the liver were also significantly reduced. Because hLAL is a secretory protein, lal(-/-) phenotypes in other compartments (eg, blood, spleen, and lung) also ameliorated, including systemic reduction of myeloid-derived suppressive cells, an increase in CD4(+) and CD8(+) T and B lymphocytes, and reduced B16 melanoma metastasis in the lung. These results support a concept that LAL in hepatocytes is a critical metabolic enzyme in controlling neutral lipid metabolism, liver homeostasis, immune response, and tumor metastasis.
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Registered trials
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