TY - JOUR
T1 - Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism
AU - Suviolahti, Elina
AU - Reue, Karen
AU - Cantor, Rita M.
AU - Phan, Jack
AU - Gentile, Massimiliano
AU - Naukkarinen, Jussi
AU - Soro-Paavonen, Aino
AU - Oksanen, Laura
AU - Kaprio, Jaakko
AU - Rissanen, Aila
AU - Salomaa, Veikko
AU - Kontula, Kimmo
AU - Taskinen, Marja Riitta
AU - Pajukanta, Päivi
AU - Peltonen, Leena
N1 - Funding Information:
We wish to warmly thank the patients for participating in this study. Dr Pertti Mustajoki and Dr Jorma Salmi are greatly appreciated for patient collection. Minna Levander is thanked for excellent technical assistance and Kaisa Silander for Sequenom expertise. This study was supported by the Finnish Cultural Foundation, Sigrid Jusélius Foundation, Finnish Heart Foundation, The Center of Excellence in Disease Genetics of the Academy of Finland, the European Commission (BM4-CT95-0662 and QLG2-CT-2002-01254), Biomedicum Helsinki Foundation, United States Public Health Service grants HL28481 and HL-70150, American Heart Association Grant 0430180 N, UCLA Medical Scientist Training Program grant GM08042, The Helsingin Sanomat Centennial Foundation.
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=31544451530&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31544451530&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddi448
DO - 10.1093/hmg/ddi448
M3 - Article
C2 - 16357106
AN - SCOPUS:31544451530
SN - 0964-6906
VL - 15
SP - 377
EP - 386
JO - Human molecular genetics
JF - Human molecular genetics
IS - 3
ER -