ALOX5AP expression, but not gene haplotypes, is associated with obesity and insulin resistance.
OBJECTIVE
Inflammation in adipose tissue may link obesity to insulin resistance and atherosclerosis. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) gene is involved in the pathogenesis of atherosclerotic cardiovascular disease (CVD). We investigated ALOX5AP expression in adipose tissue, and association of gene polymorphisms with obesity and insulin resistance.


METHODS
For gene expression analysis in adipose tissue, we studied 12 lean and 36 obese women, eight lean and 13 obese men, and nine women before and 2-4 years after gastric banding surgery. For genetic analysis, we studied 231 nonobese and 350 obese men.


RESULTS
The ALOX5AP protein, 5-lipoxygenase activating protein (FLAP), as well as 5-lipoxygenase (5LO) itself, were detected in adipocytes. The mRNA expression of ALOX5AP in subcutaneous adipose tissue was increased in obesity and normalized following weight reduction. High adipose tissue mRNA expression of ALOX5AP is associated with insulin resistance as measured by homeostasis model assessment (HOMA(IR)). ALOX5AP haplotypes that associate with CVD are not associated with obesity or insulin resistance.


CONCLUSIONS
ALOX5AP is present in adipose tissue, where its expression is associated with body weight and HOMA(IR), and may provide a link between adipose tissue, inflammation and insulin resistance. Investigated ALOX5AP haplotypes are not major primary risk factors for obesity and insulin resistance.
Kaaman
M
M
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Rydén
M
M
Axelsson
T
T
Nordström
E
E
Sicard
A
A
Bouloumié
A
A
Langin
D
D
Arner
P
P
Dahlman
I
I
D058927:5-Lipoxygenase-Activating Proteins; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger