ArticleThe Journal of clinical investigation2019
Lipin 2/3 phosphatidic acid phosphatases maintain phospholipid homeostasis to regulate chylomicron synthesis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- LPIN2 contributes to tyrosine kinase inhibitor resistance via activation of PI3K pathway.Translational lung cancer research · 2026Article
- Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity.iScience · 2026Article
- Article
- The regulation mechanism of α-linolenic acid bioavailability by flaxseed lignan macromolecules in O/W emulsions.NPJ science of food · 2026Article
- Lipin3 deficiency promotes hepatocyte ferroptosis and pyroptosis via activating JAK1-STAT3 pathway during acetaminophen induced acute liver injury.Molecular biomedicine · 2025Article
- Lipin phosphatidic acid phosphatases: Structure, function, regulation, and disease association.Advances in biological regulation · 2025Review
- Role of Extracellular Vesicles in TSC Renal Cystogenesis.International journal of molecular sciences · 2025Article
- LPIN3 promotes colorectal cancer growth by dampening intratumoral CD8Cancer immunology, immunotherapy : CII · 2025Article
- TLR4 modulates simvastatin's impact on HDL cholesterol and glycemic control.Frontiers in pharmacology · 2025Article
- The role of glycerophospholipid metabolism in feline parvovirus infected CRFK cells.Frontiers in microbiology · 2025Article
- Lipin3 deficiency aggravates cisplatin induced acute kidney injury via activating Sirt1-p21-Caspase 3-GSDME pyroptosis pathway.International journal of biological sciences · 2025Article
- Diacylglycerol Kinases and Its Role in Lipid Metabolism and Related Diseases.International journal of molecular sciences · 2024Review
- Phosphatidic acid is an endogenous negative regulator of PIEZO2 channels and mechanical sensitivity.Nature communications · 2024Article
- Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1.Frontiers of medicine · 2024Article
- Feeding activates FGF15-SHP-TFEB-mediated lipophagy in the gut.The EMBO journal · 2022Article
- Intravital lipid droplet labeling and imaging reveals the phenotypes and functions of individual macrophages in vivo.Journal of lipid research · 2022Article
- [Correlation ofZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Article
- Intestinal Deletion of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion of the Resident Stem Cell Compartment.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Phosphatidic acid phosphatase 1 impairs SARS-CoV-2 replication by affecting the glycerophospholipid metabolism pathway.International journal of biological sciences · 2022Article
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12 authors at 2 institutions in 2 countries.
Funding
Abstract
The lipin phosphatidic acid phosphatase (PAP) enzymes are required for triacylglycerol (TAG) synthesis from glycerol 3-phosphate in most mammalian tissues. The 3 lipin proteins (lipin 1, lipin 2, and lipin 3) each have PAP activity, but have distinct tissue distributions, with lipin 1 being the predominant PAP enzyme in many metabolic tissues. One exception is the small intestine, which is unique in expressing exclusively lipin 2 and lipin 3. TAG synthesis in small intestinal enterocytes utilizes 2-monoacylglycerol and does not require the PAP reaction, making the role of lipin proteins in enterocytes unclear. Enterocyte TAGs are stored transiently as cytosolic lipid droplets or incorporated into lipoproteins (chylomicrons) for secretion. We determined that lipin enzymes are critical for chylomicron biogenesis, through regulation of membrane phospholipid composition and association of apolipoprotein B48 with nascent chylomicron particles. Lipin 2/3 deficiency caused phosphatidic acid accumulation and mammalian target of rapamycin complex 1 (mTORC1) activation, which were associated with enhanced protein levels of a key phospholipid biosynthetic enzyme (CTP:phosphocholine cytidylyltransferase α) and altered membrane phospholipid composition. Impaired chylomicron synthesis in lipin 2/3 deficiency could be rescued by normalizing phospholipid synthesis levels. These data implicate lipin 2/3 as a control point for enterocyte phospholipid homeostasis and chylomicron biogenesis.
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