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Adipose Tissue Lipin-1 Expression Is Correlated with Peroxisome Proliferator-Activated Receptor Gene Expression and Insulin Sensitivity in Healthy Young Men

Departments of Human Genetics and Medicine (J.D., K.R.), David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095; and Pennington Biomedical Research Center (L.M.S., H.X., S.R.S.), Baton Rouge, Louisiana 70808

Address all correspondence and requests for reprints to: Karen Reue, University of California, Human Genetics, 6506A Gonda, 695 Charles E. Young Drive South, Los Angeles, California 90095. 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 a euglycemic-hyperinsulinemic clamp, and whole body oxygen consumption and respiratory quotient by indirect calorimetry. We performed gene expression analysis in adipose tissue samples from human subjects and from lipin-1 transgenic mice using quantitative RT-PCR.

Results: In healthy young men, lipin-1 expression was positively correlated with insulin sensitivity (R² = 0.22; P < 0.01), insulin-stimulated respiratory quotient (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 peroxisome proliferator-activated receptor (R² = 0.74; P < 1 x 10^–7), a nuclear receptor with a key role in fatty acid oxidation.

Conclusion: 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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