title: [Lipin 1 in lipid metabolism].
abstract: The gene encoding lipin 1 was identified with a positional cloning approach that localized the causative mutation in fatty liver dystrophic (fld) mice, a mouse model of lipodystrophy. The fld mouse lacks normal adipose tissue in the body, and displays metabolic dysregulation such as obesity, insulin resistance, and hypertriglyceridemia. Lipin 1 is abundantly expressed in key metabolic tissues, including adipose tissue, skeletal muscle, and liver. In the cytosol, lipin 1 acts as an Mg²⁺-dependent phosphatidate phosphatase type-1 (PAP1), catalyzing a key step in the synthesis of glycerolipids. In the nucleus, lipin 1 acts as a transcriptional coactivator through its direct interaction with peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α) and PPARα. Through two distinct functions in the nucleus and cytosol, lipin 1 modulates lipid metabolism and glucose homeostasis. Here we will discuss recent developments in our understanding of the role of lipin 1 in lipid metabolism.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan. kenji@phs.osaka-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishimoto
mesh_terms: D000818:Animals; D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D015870:Gene Expression; D006017:Glycolipids / Q000096:biosynthesis; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D052439:Lipid Metabolism Disorders / Q000235:genetics* / Q000628:therapy; D051379:Mice; D058990:Molecular Targeted Therapy; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D047493:PPAR alpha / Q000502:physiology; D000073718:Pancreatitis-Associated Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010711:Phosphatidate Phosphatase / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors; D015533:Transcriptional Activation; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D006017:Glycolipids; D009687:Nuclear Proteins; D047493:PPAR alpha; D000073718:Pancreatitis-Associated Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011506:Proteins; C000612141:REG3A protein, human; C490253:Reg3b protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase