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


METHODS
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.


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.
Donkor
Jimmy
J
University of California, Department of Human Genetics, 6506A Gonda, 695 Charles E. Young Drive South, Los Angeles, California 90095, USA.
Sparks
Lauren M
LM
Xie
Hui
H
Smith
Steven R
SR
Reue
Karen
K
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D001823:Body Composition; D015331:Cohort Studies; D005215:Fasting / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D047493:PPAR alpha / Q000096:biosynthesis* / Q000235:genetics; D010711:Phosphatidate Phosphatase; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009687:Nuclear Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase