the dyslipidemic profile of abdominal obesity , and its association with atherogenic risk [ 1 , 2 ] is attributed to insulin resistance and altered secretion of fat derived factors including fatty acids and adipokines such as adiponectin , leptin , interleukin-6 , and tumor necrosis factor - alpha . acylation - stimulating protein ( asp ) is another adipokine that was isolated based on its function as a potent fat storage factor . abundant in vivo and in vitro evidence linked asp function to enhanced triglyceride clearance by promoting fatty acid trapping and fat storage in adipocytes by activating the rate - limiting enzyme for tg synthesis , diacylglycerol acyl transferase . insulin , on the other hand , activates lipoprotein lipase releasing fatty acids for uptake by adipocytes and inhibits hormone - sensitive lipase which catalyzes fat hydrolysis from adipocytes . asp levels were shown to increase in obese and hyperlipidemic subjects [ 5 , 7 ] and decrease with weight loss and fasting [ 5 , 8 ] . subjects with a variant of the c5l2 receptor demonstrated marked reduction in asp binding associated with increased plasma tg and asp levels , and a significant reduction in asp stimulated tg synthesis and glucose transport suggestive of receptor downregulation . several studies demonstrated that increased asp levels positively correlated with increased tg levels , while a weaker correlation was found with total and ldl cholesterol or apob levels [ 11 , 12 ] . asp resistance was suggested to contribute to increased tg levels as a result of delayed asp - mediated tg clearance [ 5 , 11 , 14 , 15 ] . increased tg and low hdl - c levels , as a consequence of delayed tg clearance , are important determinants of the dyslipidemic profile associated with abdominal obesity , and the tg / hdl - c ratio is a recognized predictor of ldl size variations in serum [ 17 , 18 ] . since asp is largely implicated in enhancing fat storage and plasma tg clearance , we investigated the association of plasma asp levels with markers of abdominal obesity and its related metabolic profile including waist / hip ratio , tg , hdl - c , and other lipid profile parameters including ldl particle size which has not been investigated previously . a sample of 83 omani males was included in this study ( average age 41.8  12.1 years ) . the subjects included had a wide range of abdominal girths as indicated by waist / hip ratio : 0.751.34 . in order to compare differences in plasma asp levels between abdominally obese and nonobese men , abdominally obese subjects this cutoff point for high waist / hip ratio was selected according to the american heart association to define high risk for cardiovascular disease in men [ 1921 ] . fasting blood samples were collected in plain tubes with no anticoagulant for lipid measurements and edta tubes for asp measurements . the collection was performed in the morning , and samples were put on ice and immediately centrifuged . the serum and plasma were stored at 80c until analysis . all samples were analyzed for the fasting lipid profile , including tg , total cholesterol ( total - c ) , ( ldl - c ) , ( hdl - c ) , apolipoprotein apob , and apoa1 . analysis was performed using an automated clinical chemistry analyzer cx 7 super clinical system ( synchron ) based on enzymatic colorimetric assays for lipid parameters : tg , total - c , hdl - c , and ldl - c . analysis of samples for apoa and apob was based on immunoturbidimetry of antigen antibody reactions with the sample apoprotein detected as antigen by immage immunochemistry systems . human blood edta samples were centrifuged , the plasma was separated , and asp was assayed immediately by a sandwich elisa using a monoclonal antibody as capture antibody and a polyclonal antibody as detecting antibody , as described in detail previously . nondenaturing 3% to 16% polyacrylamide gradient gel electrophoresis ( pagge ) was performed as described previously . briefly , ldl particle size was determined on 16  cm  16  cm polyacrylamide gradient gels prepared in our laboratory . potentials were set at 125  v ( 15  min ) , 200  v ( 4  hr ) , and 300  v ( 2  hr ) . gels were fixed and stained for lipids in a solution containing oil red o in 60% ethanol at 50c for 24  hr and destained in acetic acid ( 5% ) . the gels were placed on filter paper and dried with gel drying system ( bio - rad ) for one 45 minutes at 80c . dried gels were photographed with a bioimaging system ( chemi genius ) using gene - snap program , and band densities were analyzed using gene - tools program . the program allows measurement of the migration of the bands in the gel by densitometry . ldl size was extrapolated from the relative migration of three ldl control samples and lipoprotein little a lp ( a ) that were purified by electroelution for which particle size was measured by electron microscopy . the control samples were run alongside the samples and stained with oil red o. ldl size measurements were verified from the relative migration of protein standard samples ( high molecular weight native marker kit from ge healthcare nj ) stained by coommasie blue . step - wise multiple linear regression analysis was performed to determine factors that significantly explain variations in fasting plasma asp levels . analysis was computer assisted using the spss / pc statistical program ( version 13.0 for windows ; spss , inc . , chicago , il ) . table 1 shows the correlation of asp with all measured anthropometric and lipid parameters using bivariate analysis . significant positive correlations were found for asp with waist / hip ratio , bmi , age , tg , and very low density cholesterol ( vldl - c ) levels . no correlation was found with total cholesterol , ldl - c , hdl - c , apob levels , or glucose levels . figure 1 shows a scatter plot representing the correlation of asp with waist / hip ratio for all the subjects . a significant negative correlation ( r = 0.25 , p = 0.025 ) was found between fasting plasma asp levels and ldl size , a result supported by a significant correlation of asp with tg / hdl - c ( r = 0.28 , p = 0.01 ) which is a recognized predictor of ldl size . a stepwise multiple linear regression model was set to determine the parameters that significantly predict asp variations in this study . independent variables included waist / hip ratio , bmi , age and lipid parameters : tg , total cholesterol , ldl - c , hdl - c , apoa1 , apob , and ldl size . waist / hip ratio entered the model as the highest significant predictor (  = 0.52 , p < 0.0001 ) followed by ldl size (  = 0.22 , p = 0.02 ) . waist / hip ratio explained 26.3% variation in asp levels ( as determined by the adjusted r ) , followed by ldl size where both parameters determined 30% variation in asp levels . bmi age , and all measured lipid and apoprotein parameters were excluded as nonsignificant predictors of asp levels . plasma asp levels , lipid , and anthropometric profiles were investigated for all subjects . figure 2 shows differences in asp levels between abdominally obese ( w / h  0.95 , n = 35 ) and nonobese ( w / h < 0.95 , n = 48 ) subjects . abdominally obese subjects had 62.5% increase in plasma asp levels ( p < 0.001 ) compared to nonobese subjects . metabolic alterations that accompany intraabdominal fat accumulation typically involve increased tg levels , low hdl - c levels ( increased tg / hdl - c ratio ) , formation of small dense ldl particles , and normal ldl - c levels . results in this study notably link plasma asp levels to the metabolic profile associated with abdominal obesity . asp levels were shown to be higher in males with abdominal obesity compared to nonobese subjects . asp levels showed a significant positive correlation with waist / hip ratio , tg levels , and tg / hdl ratio and negatively correlated with hdl - c levels and ldl size . consistent with previous studies , there was no correlation of asp with ldl - c or apoprotein levels [ 11 , 12 , 26 ] .   in previous studies , a significant positive association between asp and tg levels independent of bmi was shown ; however , waist / hip ratio and ldl size were not included as independent parameters in their analysis [ 11 , 14 , 27 , 28 ] . in this study , a significant positive association was found for plasma asp with tg levels however , adding waist / hip ratio and ldl size to the regression model excluded both plasma tg and bmi as significant predictors of asp levels . waist / hip ratio alone predicted 26.3% increase in asp levels , followed by ldl size together with significantly predicting 30% variation in asp levels . these marked variations suggest that waist / hip ratio , an abdominal obesity marker , surpasses the effect of plasma tg levels and all measured parameters in this study as a determinant of plasma asp variation . in order to explain increased asp levels in association with abdominal obesity , we highlight  metabolic resistance  as an important feature that may be shared between insulin and asp . it is well established that insulin resistance , reflected in increased plasma insulin levels , is an underlying feature of abdominal obesity , and a major component of the metabolic syndrome . in vitro and in vivo asp resistance , in association with increased asp and tg levels , was introduced in several studies [ 5 , 10 , 11 , 1315 ] . increased asp levels in abdominal obesity may result from decreased response of intra - abdominal ( omental ) fat to asp function . this is supported by studies showing that asp binding affinity was markedly lower in plasma membrane extracts from omental compared to subcutaneous adipose tissue , and lower in male compared to female adipose tissue . furthermore , functional studies showed that asp - mediated triglyceride synthesis was markedly lower in omental adipocytes compared to subcutaneous adipocytes . in vivo studies showed a decreased response to asp - mediated triglyceride clearance in males compared to females in humans and mice . findings in this study suggest that , with accumulation of omental fat in males , asp resistance may develop which is reflected in increased plasma asp levels and decreased plasma tg clearance . accumulation of plasma tg rich - vldl levels may therefore accelerate metabolic events that normally catalyze the conversion of vldl particles into small dense ldl particles in association with decreased hdl - c levels [ 25 , 32 , 33 ] ( figure 3 ) . one study showed no significant association between asp and waist / hip ratio in females . however , predictors of asp levels were not reported in these studies . to our knowledge , this is the first study highlighting that increased waist / hip ratio , in association with decreased ldl size , significantly determine plasma asp levels , which may link asp to atherogenic metabolic events in abdominally obese males . in conclusion , elevated asp levels in abdominal obesity , strongly predicted by waist / hip ratio , suggest that asp production by abdominal fat may be increased as a result of asp resistance , a concept proposed in previous studies [ 5 , 11 , 1315 ] . asp resistance may contribute to lipid alterations that encourage the formation of atherogenic small dense ldl particles , and therefore increase the risk of coronary artery disease ( cad ) in abdominally obese subjects . these findings highlight asp as another adipokine metabolic marker   that may contribute to further understanding of the pathophysiology of abdominal obesity and its link to cardiovascular risk in men .
the association of abdominal obesity with cardiovascular risk is often linked to altered secretion of adipose - derived factors and an abnormal lipid profile including formation of atherogenic small dense low density lipoprotein particles ( sdldl ) . 
 acylation - stimulating protein ( asp ) is an adipose - derived hormone that exhibits potent lipogenic effects . 
 plasma asp levels increase in obesity ; however , the association of asp levels with body fat distribution is not yet established , and no study to date has investigated the association of asp with ldl size . in this study , we examined the association of asp levels with abdominal obesity measures and the lipid profile including ldl size in 83 men with a wide range of abdominal girths . 
 regression analysis showed that waist / hip ratio was the main predictor of asp levels (  = 0.52 , p < 0.0001 ) , significantly followed by decreased ldl size . 
 bmi and tg levels , although positively correlated with asp levels , were excluded as significant predictors in regression analysis . 
 no correlation was found with ldl - c or apob levels . 
 asp levels were 62.5% higher in abdominally obese compared to nonobese men . 
 waist / hip ratio presenting as the main predictor of asp levels , suggests increased asp production by abdominal fat which , as proposed previously , may result from resistance to asp function causing delayed tg clearance and subsequent formation of atherogenic sdldl .