| First Author | Péterfy M | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 38 | Pages | 32883-9 |
| PubMed ID | 16049017 | Mgi Jnum | J:102156 |
| Mgi Id | MGI:3607005 | Doi | 10.1074/jbc.M503885200 |
| Citation | Peterfy M, et al. (2005) Alternatively spliced lipin isoforms exhibit distinct expression pattern, subcellular localization, and role in adipogenesis. J Biol Chem 280(38):32883-9 |
| abstractText | We recently identified mutations in the Lpin1 (lipin) gene to be responsible for lipodystrophy in the fatty liver dystrophy (fld) mouse strain. Previous studies revealed that lipin plays a critical role in adipogenesis, explaining the adipose-deficient phenotype of the fld mouse. In the current study, we demonstrate that alternative mRNA splicing generates two lipin isoforms, lipin-alpha and lipin-beta, which are differentially expressed during adipocyte differentiation. Lipin-alpha expression peaks at day 2 of 3T3-L1 cell differentiation, after which its levels gradually decrease. In contrast, lipin-beta expression is transiently elevated at 10 h, followed by a drop to background levels at 20 h and a gradual increase between days 2 and 6 of differentiation. The two lipin isoforms also exhibit differences in subcellular localization. Lipin-alpha is predominantly nuclear, whereas lipin-beta is primarily located in the cytoplasm of 3T3-L1 adipocytes, suggesting distinct cellular functions. Using primary mouse embryonic fibroblasts expressing either lipin-alpha or lipin-beta, we demonstrate functional differences between the two isoforms. Whereas lipin-alpha is required for adipocyte differentiation, the predominant effect of lipin-beta expression is the induction of lipogenic genes. In vivo, overexpression of lipin-beta specifically in mature adipocytes leads to elevated expression of lipogenic genes and adipocyte hypertrophy, confirming a role of lipin-beta in the regulation of lipogenesis. In conclusion, our data suggest that the two lipin isoforms have distinct, but complementary, functions in adipogenesis, with lipin-alpha playing a primary role in differentiation and lipin-beta being predominantly involved in lipogenesis. |
