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This version published online on October 9, 2007
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-1535
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Submitted on July 10, 2007
Accepted on October 1, 2007

Adipose tissue lipin-1 expression is correlated with ppar{alpha} gene expression and insulin sensitivity in healthy young men

Jimmy Donkor, Lauren M. Sparks, Hui Xie, Steven R. Smith, and Karen Reue*

Departments of Human Genetics and Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, and Pennington Biomedical Research Center, Baton Rouge, LA 70808

* To whom correspondence should be addressed. E-mail: reuek{at}ucla.edu.

Context: Lipin-1 functions in adipocyte triglyceride biosynthesis and in the regulation of gene expression, both of which may influence metabolic homeostasis.

Objective: Our objective was to determine whether variations in adipose tissue lipin-1 expression levels influence insulin sensitivity and gene expression in young, healthy human subjects.

Design and Subjects: In 56 healthy young men (22.6 ± 3.2 yr; 26.4 ± 4.1 kg/m2) we determined insulin sensitivity by euglycemic-hyperinsulinemic clamp, and whole body oxygen consumption and respiratory quotient (RQ) by indirect calorimetry. We performed gene expression analysis in adipose tissue samples from human subjects and from lipin-1 transgenic mice using qRT-PCR.

Results: In healthy young men, lipin-1 expression was positively correlated with insulin sensitivity (R2 = 0.22; P < 0.01), insulin-stimulated RQ (R2 = 0.16; P < 0.01), and maximal oxygen consumption during exercise (R2 = 0.16; P < 0.01). Lipin-1 mRNA levels were also correlated with expression of genes involved in lipid oxidation, uptake, and lipolysis, both in humans and in lipin-1 transgenic mice. The strongest correlation occurred between lipin-1 and PPAR{alpha} (R2 = 0.74; P < 1 x 10-7), a nuclear receptor with a key role in fatty acid oxidation.

Conclusions: Lipin-1 expression levels in adipose tissue of healthy young subjects and in mice are correlated with a favorable metabolic profile and expression of fatty acid oxidation genes.




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