J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M600272-JLR200 on October 11, 2006

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Journal of Lipid Research, Vol. 48, 201-206, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology


Patient-Oriented Research

A role of lipin in human obesity and insulin resistance: relation to adipocyte glucose transport and GLUT4 expression

Vanessa van Harmelen, Mikael Rydén, Eva Sjölin and Johan Hoffstedt1

Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Published, JLR Papers in Press, October 11, 2006.

1 To whom correspondence should be addressed. e-mail: johan.hoffstedt{at}ki.se


ABSTRACT

The mouse lipin gene, Lpin1, is important for adipose tissue development and is a candidate gene for insulin resistance. Here, we investigate the adipose tissue expression levels of the human LPIN1 gene in relation to various clinical variables as well as adipocyte function. LPIN1 gene expression was induced at an early step in human preadipocyte differentiation in parallel with peroxisome proliferator-activated receptor {gamma}. Lipin mRNA levels were higher in fat cells than in adipose tissue segments but showed no difference between subcutaneous and omental depots. Moreover, LPIN1 expression levels were reduced in obesity, improved following weight reduction in obese subjects, and were downregulated in women with the metabolic syndrome. 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). We show that body fat accumulation is a major regulator of human adipose LPIN1 expression and suggest a role of LPIN1 in human preadipocyte as well as mature adipocyte function.

Supplementary key words adipogenesis • adipose tissue • fat cell • metabolic syndrome • mRNA

Abbreviations: BMI, body mass index; GPDH, glycerol-3-phosphate dehydrogenase; HOMA, homeostasis model assessment algorithm; PPAR{gamma}2, peroxisome proliferator-activated receptor {gamma} transcript variant 2


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