ArticleProceedings of the National Academy of Sciences of the United States of America2012
Mouse lipin-1 and lipin-2 cooperate to maintain glycerolipid homeostasis in liver and aging cerebellum.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 134 citations in OpenAlex.
- Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity.iScience · 2026Article
- The dynamic regulatory network of phosphatidic acid metabolism: a spotlight on substrate cycling between phosphatidic acid and diacylglycerol.Biochemical Society transactions · 2024Review
- Rhythms in lipid droplet content driven by a metabolic oscillator are conserved throughout evolution.Cellular and molecular life sciences : CMLS · 2024Article
- Cerebellum and Aging: Update and Challenges.Aging and disease · 2024Review
- LPIN2 is the phosphatase dominating the penultimate step of neutral lipid biosynthesis inmicroPublication biology · 2024Article
- Role of lipins in cardiovascular diseases.Lipids in health and disease · 2023Review
- The eQTL colocalization and transcriptome-wide association study identify potentially causal genes responsible for economic traits in Simmental beef cattle.Journal of animal science and biotechnology · 2023Article
- DYT-Frontiers in neuroscience · 2023Review
- Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.Circulation. Genomic and precision medicine · 2022Article
- Pathophysiology, clinical manifestations and current management of IL-1 mediated monogenic systemic autoinflammatory diseases, a literature review.Pediatric rheumatology online journal · 2022Review
- Lipin 1 modulates mRNA splicing during fasting adaptation in liver.JCI insight · 2021Article
- Majeed Syndrome: A Review of the Clinical, Genetic and Immunologic Features.Biomolecules · 2021Review
- Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity.Biomolecules · 2020Review
- Whole Lotta Lipids-from HCV RNA Replication to the Mature Viral Particle.International journal of molecular sciences · 2020Review
- Article
- The Function of Lipin in the Wing Development ofInternational journal of molecular sciences · 2019Article
- Article
- CHP1 Regulates Compartmentalized Glycerolipid Synthesis by Activating GPAT4.Molecular cell · 2019Article
- Mammalian lipin phosphatidic acid phosphatases in lipid synthesis and beyond: metabolic and inflammatory disorders.Journal of lipid research · 2019Review
- Lipin 2/3 phosphatidic acid phosphatases maintain phospholipid homeostasis to regulate chylomicron synthesis.The Journal of clinical investigation · 2019Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
The three lipin phosphatidate phosphatase (PAP) enzymes catalyze a step in glycerolipid biosynthesis, the conversion of phosphatidate to diacylglycerol. Lipin-1 is critical for lipid synthesis and homeostasis in adipose tissue, liver, muscle, and peripheral nerves. Little is known about the physiological role of lipin-2, the predominant lipin protein present in liver and the deficient gene product in the rare disorder Majeed syndrome. By using lipin-2-deficient mice, we uncovered a functional relationship between lipin-1 and lipin-2 that operates in a tissue-specific and age-dependent manner. In liver, lipin-2 deficiency led to a compensatory increase in hepatic lipin-1 protein and elevated PAP activity, which maintained lipid homeostasis under basal conditions, but led to diet-induced hepatic triglyceride accumulation. As lipin-2-deficient mice aged, they developed ataxia and impaired balance. This was associated with the combination of lipin-2 deficiency and an age-dependent reduction in cerebellar lipin-1 levels, resulting in altered cerebellar phospholipid composition. Similar to patients with Majeed syndrome, lipin-2-deficient mice developed anemia, but did not show evidence of osteomyelitis, suggesting that additional environmental or genetic components contribute to the bone abnormalities observed in patients. Combined lipin-1 and lipin-2 deficiency caused embryonic lethality. Our results reveal functional interactions between members of the lipin family in vivo, and a unique role for lipin-2 in central nervous system biology that may be particularly important with advancing age. Additionally, as has been observed in mice and humans with lipin-1 deficiency, the pathophysiology in lipin-2 deficiency is associated with dysregulation of lipid intermediates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.