The Role of Lipin Proteins in Lipid Storage and Metabolism

Abstract

The three members of the lipin protein family (lipin‐1, lipin‐2 and lipin‐3) are Mg2+dependent phosphatidate phosphatase (PAP) enzymes, which catalyze a key reaction in glycerolipid biosynthesis. Lipin‐1 has also been shown to act as a transcriptional coactivator to modulate gene expression in response to fasting in the liver. Each of the lipin genes exhibits a distinct tissue expression pattern suggesting unique physiological functions. Lipin‐1 is prominently expressed in adipose tissue and muscle, and mutations in the lipin‐1 gene cause lipodystrophy in the mouse and myoglobinuria in humans. In contrast, lipin‐2 is most prominently expressed in tissues such as liver, kidney, brain, and lung. Mutations in human lipin‐2 cause Majeed syndrome, an inflammatory disorder characterized by osteomyelitis, anemia, and cutaneous inflammation, but the mechanism underlying this phenotype is not understood. To address questions concerning the roles of each lipin family member in normal physiology and disease we have developed mutant mouse models for each of the lipin family members. Characterization of their phenotypes demonstrates unique, but interacting, roles for the lipin proteins in lipid storage and metabolism.