Growing evidence links the three mammalian lipin proteins, i.e., lipin-1, lipin-2 and lipin-3, to metabolic and cardiovascular diseases such as noninsulin-dependent diabetes mellitus and atherosclerosis. Lipin proteins play a dual function in lipid metabolism by acting as phosphatidate phosphatase (PAP) enzymes and as transcriptional regulators. Genetic variants within the human LPIN1 and LPIN2 genes are associated with metabolic syndromes. The fatty liver dystrophy (fld) mice carrying mutations within the Lpin1 gene display life-long deficiency in adipogenesis, insulin resistance, neonatal hepatosteatosis and hypertriglyceridemia, as well as increased atherosclerosis susceptibility. Cell culture studies show that hepatic lipin-1 expression is selectively stimulated by glucocorticoids and repressed by insulin, and its subcellular localization governs the assembly and secretion of very low density lipoproteins (VLDL). In noninsulin-dependent diabetes, glucocorticoid signals lead to dyslipidemia characterized by overproduction of VLDL and atherogenic remnants. This puts lipin-1 as a key integrator of hormonal signals to the liver in diabetic dyslipidemia. This review summarizes the current understanding of the role that hepatic lipin-1 plays in the synthesis, storage and compartmentalization of glycerolipids, and highlights the lipid metabolic consequences associated with dysregulated lipin expression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbalip.2010.07.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Salinity stress impairs disease resistance in white shrimp, Penaeus vannamei through AMPK pathway, ameliorated by dietary glucose-mediated energy homeostasis.
Comp Biochem Physiol A Mol Integr Physiol
January 2025
Department of Aquaculture, National Pingtung University of Science and Technology, Pingtung 912, Taiwan. Electronic address:
This study presents a comprehensive examination of the physiological adaptations of white shrimp (Penaeus vannamei) to low-salinity conditions and evaluates the effects of supplementing dietary glucose on disease resistance. Compared to the control group, shrimp cultured at a salinity of 4 psu exhibit significantly elevated expression levels of adenosine 5'-monophosphate-activated protein kinase (AMPK) in the hepatopancreas, which leads to increased energy expenditure and a corresponding reduction in resistance to infection by Vibrio alginolyticus. The suppression of AMPK via dsAMPK treatment markedly enhances disease resistance.
View Article and Find Full Text PDFInvestigating the Effect of Galbanic Acid on Lipin-1 and Lipin-2 Genes in Fatty Liver Cells with Palmitate.
Adv Biomed Res
November 2024
Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Background: Non-alcoholic fatty liver disease is related to lipid accumulation and inflammation. Considering the role of lipin-1 and lipin-2 in fat homeostasis and inflammation, this study aimed to explore the effect of galbanic acid (Gal) and resveratrol (RSV) on alterations in the gene expression levels and protein abundance of lipin-1 and lipin-2 in HepG2 liver cells lipid-enriched with palmitate (Pal).
Materials And Methods: HepG2 cells were subjected to different amounts of Gal and RSV for 24 hours in the presence of Pal to induce lipid accumulation.
Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium.
FASEB J
December 2024
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Dysregulated lipid metabolism, characterized by the accumulation of lipid deposits on Bruch's membrane and in drusen, is considered a key pathogenic event in age-related macular degeneration (AMD). The imbalance of lipid production, usage, and transport in local tissues, particularly in the retinal pigment epithelium (RPE), is increasingly recognized as crucial in AMD development. However, the molecular mechanisms governing lipid metabolism in the RPE remain elusive.
View Article and Find Full Text PDFThe antidepressant drug sertraline is a novel inhibitor of yeast Pah1 and human lipin 1 phosphatidic acid phosphatases.
J Lipid Res
January 2025
Department of Food Science, Rutgers University, New Brunswick, NJ, USA; Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ, USA. Electronic address:
Article Synopsis
- Phosphatidic acid phosphatase (PAP) is an important enzyme involved in lipid metabolism, converting phosphatidic acid into diacylglycerol, which is vital for synthesizing fats and cell membranes.
- Researchers discovered that the antidepressant sertraline inhibits PAP activity in yeast and human cells, working through a noncompetitive mechanism and showing stronger inhibition than a common PAP inhibitor, propranolol.
- Molecular docking studies indicate that sertraline interacts with non-catalytic parts of the enzyme, and tests in yeast demonstrate that overexpressing PAP can counteract the inhibitory effects of sertraline on yeast growth and lipid content.
Scopoletin ameliorates hyperlipidemia and hepatic steatosis via AMPK, Nrf2/HO-1 and NF-κB signaling pathways.
Biochem Pharmacol
January 2025
Key Laboratory of Natural Medicines of Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China. Electronic address:
Scopoletin (SC) is one of the important phenolic coumarin constituents derived from many edible plants and fruits, and exerts a wide range of biological activities. In the present study, we investigated the effects of SC on tyloxapol (TY)-induced hyperlipidemia and hepatic steatosis in C57BL/6j mice and free fatty acid (FFA) 0.5 mM-stimulated lipid accumulation in human L02 cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!