Adipose tissue lipin-1 expression is correlated with peroxisome proliferator-activated receptor alpha gene expression and insulin sensitivity in healthy young men.

Journal of Clinical Endocrinology and Metabolism

PubMedID: 17925338

Donkor J, Sparks LM, Xie H, Smith SR, Reue K. 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. 2008;93(1):233-9.
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 alpha (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.