Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism

Department of Dental Public Health, University of Helsinki, Helsinki, Uusimaa, Finland
Human Molecular Genetics (Impact Factor: 6.68). 03/2006; 15(3):377-86. DOI: 10.1093/hmg/ddi448
Source: PubMed

ABSTRACT Recent studies in the mouse have demonstrated that variations in lipin expression levels in adipose tissue have marked effects on adipose tissue mass and insulin sensitivity. 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. Here, we investigated the effects of genetic variation in lipin levels on glucose homeostasis across species by analyzing lipin transcript levels in human and mouse adipose tissues. A strong negative correlation was observed between lipin mRNA levels and fasting glucose and insulin levels, as well as an indicator of insulin resistance (HOMA-IR), in both mice and humans. We subsequently analyzed the allelic diversity of the LPIN1 gene in dyslipidemic Finnish families, as well as in a case-control sample of obese (n = 477) and lean (n = 821) individuals. Alleles were defined by genotyping seven single nucleotide polymorphisms (SNPs) of the critical DNA region over the LPIN1 gene. Intragenic SNPs and corresponding allelic haplotypes exhibited associations with serum insulin levels and body mass index (P = 0.002-0.04). 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.

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    • "In accordance with the reports from natural human population, in our experiment chicken hepatic Lpin1 gene mRNA expression level presented significantly negative correlation with abdominal adipose deposition (AFR; P , 0.01). It was reported that Lpin1 mRNA expression had a strong negative correlation with GLU and INS levels in mouse and human, TG levels in human (Suviolahti et al., 2006). Lpin1 "
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    • "Regarding human obesity, very few reports on human LPIN1 gene expression have been performed, suggesting a positive association with insulin sensitivity [12] [13] [14] and a negative one with body mass index (BMI) [13] [14]. On the other hand, human immunodeficiency virus (HIV)-infected patients who developed lipodystrophy had lower LPIN1 messenger RNA (mRNA) levels than those without lipodystrophy , in line with findings in the fld animal model [15]. "
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