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Gene Review

Lpin1  -  lipin 1

Mus musculus

Synonyms: 4631420P06, Fatty liver dystrophy protein, Fld, Kiaa0188, Lipin-1, ...
 
 
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Disease relevance of Lpin1

 

High impact information on Lpin1

  • Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin [2].
  • However, several such genes, including SREBP-1, SREBP-2, and Lpin1, are also expressed in the endoneurium [4].
  • We find that Lpin1 null mutations lead to lipoatrophy of the epineurium, and to the dysregulation of a battery of genes required for the regulation of storage lipid metabolism in both the endoneurium and peri/epineurium [4].
  • Lipin is the product of the gene that is mutated in fatty liver dystrophy (fld) mice [Peterfy, M., Phan, J., Xu, P. & Reue, K (2001) Nat. Genet. 27, 121-124], which exhibit several phenotypic abnormalities including hyperlipidemia, defects in adipocyte differentiation, impaired glucose tolerance, and slow growth [5].
  • The results suggest that insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity [6].
 

Chemical compound and disease context of Lpin1

 

Biological context of Lpin1

 

Anatomical context of Lpin1

  • Thus, we conclude that lipin expression is required prior to PPARgamma during adipocyte differentiation [1].
  • Consistent with a requirement for lipin expression upstream of PPARgamma, differentiation of lipin-deficient mouse embryonic fibroblasts could be rescued by ectopic expression of PPARgamma [1].
  • Mutations in the Lpin1 gene (encoding lipin) cause the lipodystrophy (adipose tissue deficiency) of the fld mouse, but the underlying mechanism has been unclear [11].
  • These data suggest that the fld mutation is associated with an abnormality of myelin formation (dysmyelination) as well as demyelination and axonal degeneration that persists despite apparent resolution of the neonatal hypertriglyceridemia and associated lipase abnormalities [3].
  • Furthermore, two axon-specific proteins, neurofilament 68K and growth-associated 43 protein, display altered expression in adult fld/fld sciatic nerves [3].
 

Associations of Lpin1 with chemical compounds

 

Regulatory relationships of Lpin1

 

Other interactions of Lpin1

 

Analytical, diagnostic and therapeutic context of Lpin1

  • High performance thin-layer chromatography revealed deficiencies in phospholipids, glycosphingolipids, and some neutral lipids in fld/fld sciatic nerves harvested during the first several months of life (compared to their +/? littermates) [3].
  • To better characterize the biochemical basis for the development of fatty liver in fld mice, we compared protein expression patterns in the fatty liver of fld mice and in the liver of phenotypically normal (wild-type) littermates using quantitative two-dimensional gel electrophoresis [9].
  • After treatment of the impaired glucose-tolerant subjects with insulin sensitizers for 10 weeks, pioglitazone (but not metformin) resulted in a 60% increase in the insulin sensitivity index (S(i)) and a 32% decrease in IMCLs (both P < 0.01), along with an increase in lipin-beta (but not lipin-alpha) expression by 200% (P < 0.005) [18].

References

  1. Lipin expression preceding peroxisome proliferator-activated receptor-gamma is critical for adipogenesis in vivo and in vitro. Phan, J., Péterfy, M., Reue, K. J. Biol. Chem. (2004) [Pubmed]
  2. Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Péterfy, M., Phan, J., Xu, P., Reue, K. Nat. Genet. (2001) [Pubmed]
  3. Characterization of the peripheral neuropathy in neonatal and adult mice that are homozygous for the fatty liver dystrophy (fld) mutation. Langner, C.A., Birkenmeier, E.H., Roth, K.A., Bronson, R.T., Gordon, J.I. J. Biol. Chem. (1991) [Pubmed]
  4. Local regulation of fat metabolism in peripheral nerves. Verheijen, M.H., Chrast, R., Burrola, P., Lemke, G. Genes Dev. (2003) [Pubmed]
  5. Insulin-stimulated phosphorylation of lipin mediated by the mammalian target of rapamycin. Huffman, T.A., Mothe-Satney, I., Lawrence, J.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Insulin controls subcellular localization and multisite phosphorylation of the phosphatidic Acid phosphatase, lipin 1. Harris, T.E., Huffman, T.A., Chi, A., Shabanowitz, J., Hunt, D.F., Kumar, A., Lawrence, J.C. J. Biol. Chem. (2007) [Pubmed]
  7. Genetic, physical, and transcript map of the fld region on mouse chromosome 12. Péterfy, M., Phan, J., Oswell, G.M., Xu, P., Reue, K. Genomics (1999) [Pubmed]
  8. The fatty liver dystrophy (fld) mutation. A new mutant mouse with a developmental abnormality in triglyceride metabolism and associated tissue-specific defects in lipoprotein lipase and hepatic lipase activities. Langner, C.A., Birkenmeier, E.H., Ben-Zeev, O., Schotz, M.C., Sweet, H.O., Davisson, M.T., Gordon, J.I. J. Biol. Chem. (1989) [Pubmed]
  9. The fatty liver dystrophy mutant mouse: microvesicular steatosis associated with altered expression levels of peroxisome proliferator-regulated proteins. Rehnmark, S., Giometti, C.S., Slavin, B.G., Doolittle, M.H., Reue, K. J. Lipid Res. (1998) [Pubmed]
  10. Naturally occurring mutations in mice affecting lipid transport and metabolism. Reue, K., Doolittle, M.H. J. Lipid Res. (1996) [Pubmed]
  11. The fat and thin of lipin. Reitman, M.L. Cell metabolism. (2005) [Pubmed]
  12. Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis. LaRosa, P.C., Miner, J., Xia, Y., Zhou, Y., Kachman, S., Fromm, M.E. Physiol. Genomics (2006) [Pubmed]
  13. Genome-wide Expression Analysis Reveals 100 Adrenal Gland-dependent Circadian Genes in the Mouse Liver. Oishi, K., Amagai, N., Shirai, H., Kadota, K., Ohkura, N., Ishida, N. DNA Res. (2005) [Pubmed]
  14. Lipin deficiency impairs diurnal metabolic fuel switching. Xu, J., Lee, W.N., Phan, J., Saad, M.F., Reue, K., Kurland, I.J. Diabetes (2006) [Pubmed]
  15. Lipin, a lipodystrophy and obesity gene. Phan, J., Reue, K. Cell metabolism. (2005) [Pubmed]
  16. The fld mutation maps near to but distinct from the Apob locus on mouse chromosome 12. Rowe, L.B., Sweet, H.O., Gordon, J.I., Birkenmeier, E.H. Mamm. Genome (1996) [Pubmed]
  17. Acads gene deletion in BALB/cByJ mouse strain occurred after 1981 and is not present in BALB/cByJ-fld mutant mice. Reue, K., Cohen, R.D. Mamm. Genome (1996) [Pubmed]
  18. Lipin Expression Is Attenuated in Adipose Tissue of Insulin-Resistant Human Subjects and Increases With Peroxisome Proliferator-Activated Receptor {gamma} Activation. Yao-Borengasser, A., Rasouli, N., Varma, V., Miles, L.M., Phanavanh, B., Starks, T.N., Phan, J., Spencer, H.J., McGehee, R.E., Reue, K., Kern, P.A. Diabetes (2006) [Pubmed]
 
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