Human Molecular Genetics Advance Access published online on December 15, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi448
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Molecular Medicine, National Public Health Institute, and Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, Finland; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA
* To whom correspondence should be addressed. 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 tissue. 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 (BMI) (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.
Received August 5, 2005
Revised December 3, 2005
Accepted December 3, 2005
Article
Cross-Species Analyses Implicate Lipin 1 Involvement in Human Glucose Metabolism
Elina Suviolahti 1,
Karen Reue 2,
Rita M. Cantor 3,
Jack Phan 2,
Massimilliano Gentile 4,
Jussi Naukkarinen 5,
Aino Soro-Paavonen 6,
Laura Oksanen 6,
Jaakko Kaprio 7,
Aila Rissanen 8,
Veikko Salomaa 9,
Kimmo Kontula 6,
Marja-Riitta Taskinen 6,
Päivi Pajukanta 2,
and
Leena Peltonen 10 *
2 Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA
3 Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA; Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, USA
4 Department of Molecular Medicine, National Public Health Institute, and Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, Finland; Biomedicum Bioinformatics Unit, University of Helsinki, Finland
5 Department of Molecular Medicine, National Public Health Institute, and Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, Finland
6 Department of Medicine, University of Helsinki, Finland
7 Finnish Twin Cohort Study, Department of Public Health, University of Helsinki, Finland; Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland
8 Obesity Research Unit, Helsinki University Central Hospital, Helsinki, Finland
9 Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland
10 Department of Molecular Medicine, National Public Health Institute, and Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, P.O. Box 104, 00251, Helsinki, Finland; Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA; The Broad Institute, MIT, Boston, MA,USA
Leena Peltonen, E-mail: leena.peltonen{at}ktl.fi
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. S. Douglas, J. L. Moran, J. R. Bermingham Jr, X.-J. Chen, D. N. Brindley, B. Soliven, D. R. Beier, and B. Popko Concurrent Lpin1 and Nrcam Mouse Mutations Result in Severe Peripheral Neuropathy with Transitory Hindlimb Paralysis J. Neurosci., September 30, 2009; 29(39): 12089 - 12100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Takeuchi and K. Reue Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1195 - E1209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Reue and J. R. Dwyer Lipin proteins and metabolic homeostasis J. Lipid Res., April 1, 2009; 50(Supplement): S109 - S114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Mlinar, M. Pfeifer, E. Vrtacnik-Bokal, M. Jensterle, and J. Marc Decreased lipin 1{beta} expression in visceral adipose tissue is associated with insulin resistance in polycystic ovary syndrome Eur. J. Endocrinol., December 1, 2008; 159(6): 833 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Reue and D. N. Brindley Thematic Review Series: Glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism J. Lipid Res., December 1, 2008; 49(12): 2493 - 2503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Fawcett, N. Grimsey, R. J.F. Loos, E. Wheeler, A. Daly, M. Soos, R. Semple, H. Syddall, C. Cooper, S. Siniossoglou, et al. Evaluating the Role of LPIN1 Variation in Insulin Resistance, Body Weight, and Human Lipodystrophy in U.K. Populations Diabetes, September 1, 2008; 57(9): 2527 - 2533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Zhang, L. O'Loughlin, D. N. Brindley, and K. Reue Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis J. Lipid Res., July 1, 2008; 49(7): 1519 - 1528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Donkor, L. M. Sparks, H. Xie, S. R. Smith, and K. Reue Adipose Tissue Lipin-1 Expression Is Correlated with Peroxisome Proliferator-Activated Receptor {alpha} Gene Expression and Insulin Sensitivity in Healthy Young Men J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 233 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wiedmann, M. Fischer, M. Koehler, K. Neureuther, G. Riegger, A. Doering, H. Schunkert, C. Hengstenberg, and A. Baessler Genetic Variants Within the LPIN1 Gene, Encoding Lipin, Are Influencing Phenotypes of the Metabolic Syndrome in Humans Diabetes, January 1, 2008; 57(1): 209 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Reue and J. Donkor Genetic Factors in Type 2 Diabetes: All in the (Lipin) Family Diabetes, December 1, 2007; 56(12): 2842 - 2843. [Full Text] [PDF]
|
|
|
|
|
|
Y. S. Aulchenko, J. Pullen, W. P. Kloosterman, M. Yazdanpanah, A. Hofman, N. Vaessen, P. J.L.M. Snijders, D. Zubakov, I. Mackay, M. Olavesen, et al. LPIN2 Is Associated With Type 2 Diabetes, Glucose Metabolism, and Body Composition Diabetes, December 1, 2007; 56(12): 3020 - 3026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Croce, J. C. Eagon, L. L. LaRiviere, K. M. Korenblat, S. Klein, and B. N. Finck Hepatic Lipin 1{beta} Expression Is Diminished in Insulin-Resistant Obese Subjects and Is Reactivated by Marked Weight Loss Diabetes, September 1, 2007; 56(9): 2395 - 2399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yatsu, N. Mizuki, N. Hirawa, A. Oka, N. Itoh, T. Yamane, M. Ogawa, T. Shiwa, Y. Tabara, S. Ohno, et al. High-Resolution Mapping for Essential Hypertension Using Microsatellite Markers Hypertension, March 1, 2007; 49(3): 446 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Donkor, M. Sariahmetoglu, J. Dewald, D. N. Brindley, and K. Reue Three Mammalian Lipins Act as Phosphatidate Phosphatases with Distinct Tissue Expression Patterns J. Biol. Chem., February 9, 2007; 282(6): 3450 - 3457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. van Harmelen, M. Ryden, E. Sjolin, and J. Hoffstedt A role of lipin in human obesity and insulin resistance: relation to adipocyte glucose transport and GLUT4 expression J. Lipid Res., January 1, 2007; 48(1): 201 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, W.N. P. Lee, J. Phan, M. F. Saad, K. Reue, and I. J. Kurland Lipin Deficiency Impairs Diurnal Metabolic Fuel Switching Diabetes, December 1, 2006; 55(12): 3429 - 3438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J van Erk, W. A. Blom, B. van Ommen, and H. F. Hendriks High-protein and high-carbohydrate breakfasts differentially change the transcriptome of human blood cells. Am. J. Clinical Nutrition, November 1, 2006; 84(5): 1233 - 1241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yao-Borengasser, N. Rasouli, V. Varma, L. M. Miles, B. Phanavanh, T. N. Starks, J. Phan, H. J. Spencer III, R. E. McGehee Jr., K. Reue, et al. Lipin Expression Is Attenuated in Adipose Tissue of Insulin-Resistant Human Subjects and Increases With Peroxisome Proliferator-Activated Receptor {gamma} Activation. Diabetes, October 1, 2006; 55(10): 2811 - 2818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Reue and L. Vergnes Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Approaches to lipid metabolism gene identification and characterization in the postgenomic era J. Lipid Res., September 1, 2006; 47(9): 1891 - 1907. [Abstract] [Full Text] [PDF]
|
|