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

Abstract

Lipin-1 functions in adipocyte triglyceride biosynthesis and in the regulation of gene expression, both of which may influence metabolic homeostasis. 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. 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. 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 alpha (R2 = 0.74; P < 1 x 10(-7)), a nuclear receptor with a key role in fatty acid oxidation. 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.