title: Cross-species analyses implicate Lipin 1 involvement in human glucose metabolism.
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.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute.
authors.forename: Elina
authors.initials: E
authors.lastname: Suviolahti
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Jack
authors.initials: J
authors.lastname: Phan
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Gentile
authors.forename: Jussi
authors.initials: J
authors.lastname: Naukkarinen
authors.forename: Aino
authors.initials: A
authors.lastname: Soro-Paavonen
authors.forename: Laura
authors.initials: L
authors.lastname: Oksanen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001706:Biopsy; D016022:Case-Control Studies; D050171:Dyslipidemias / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics; D010711:Phosphatidate Phosphatase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013851:Thinness / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase; D005947:Glucose