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LPIN1  -  lipin 1

Homo sapiens

Synonyms: KIAA0188, Lipin-1, Phosphatidate phosphatase LPIN1
 
 
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Disease relevance of LPIN1

 

High impact information on LPIN1

  • Our results indicate that lipin is required for normal adipose tissue development, and provide a candidate gene for human lipodystrophy [4].
  • Consistent with the observed reduction of adipose tissue mass in fld and fld(2J)mice, wild-type Lpin1 mRNA is expressed at high levels in adipose tissue and is induced during differentiation of 3T3-L1 pre-adipocytes [4].
  • When immunoblots were prepared with lipin antibodies, both endogenous adipocyte lipin and recombinant lipin overexpressed in HEK293 cells appeared as bands ranging in apparent M(r) from 120,000 to 140,000 [5].
  • Insulin-stimulated phosphorylation of lipin mediated by the mammalian target of rapamycin [5].
  • Alleles were defined by genotyping seven single nucleotide polymorphisms (SNPs) of the critical DNA region over the LPIN1 gene [6].
 

Biological context of LPIN1

  • LPIN1 gene expression was induced at an early step in human preadipocyte differentiation in parallel with peroxisome proliferator-activated receptor gamma [1].
  • These results suggest that increased adipogenesis and/or lipogenesis in subcutaneous fat, mediated by the LPIN1 gene, may prevent lipotoxicity in muscle, leading to improved insulin sensitivity [3].
  • In the mouse, lipin deficiency prevents normal adipose tissue development, resulting in lipodystrophy and insulin resistance, whereas excess lipin levels promote fat accumulation and insulin sensitivity [6].
  • Both the expression levels in adipose tissue across species and genetic data in human study samples highlight the importance of lipin in glucose homeostasis and imply that allelic variants of this gene have significance in human metabolic traits [6].
  • Expressed sequence tag mapping and exon trapping identified three transcripts within the critical interval: Ctla2b, which encodes a cysteine protease inhibitor, and mouse homologs of KIAA0188 and KIAA0575, two long human transcripts of unknown function [7].
 

Anatomical context of LPIN1

 

Associations of LPIN1 with chemical compounds

  • With respect to adipocyte function, adipose LPIN1 gene expression was strongly associated with both basal and insulin-mediated subcutaneous adipocyte glucose transport as well as mRNA levels of glucose transporter 4 (GLUT4) [1].
  • Hence, high adipose tissue lipin expression is found in insulin-sensitive subjects, and lipin-beta expression increases following treatment with pioglitazone [3].
  • 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) [3].

References

  1. A role of lipin in human obesity and insulin resistance: relation to adipocyte glucose transport and GLUT4 expression. van Harmelen, V., Ryd??n, M., Sj??lin, E., Hoffstedt, J. J. Lipid Res. (2007) [Pubmed]
  2. Identification of single-nucleotide polymorphisms in the human LPIN1 gene. Cao, H., Hegele, R.A. J. Hum. Genet. (2002) [Pubmed]
  3. 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]
  4. 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]
  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. Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism. Suviolahti, E., Reue, K., Cantor, R.M., Phan, J., Gentile, M., Naukkarinen, J., Soro-Paavonen, A., Oksanen, L., Kaprio, J., Rissanen, A., Salomaa, V., Kontula, K., Taskinen, M.R., Pajukanta, P., Peltonen, L. Hum. Mol. Genet. (2006) [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]
 
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