the main study sample included 190 women aged 33 to 68 years recruited through the elective surgery schedule of the gynecology unit at the laval university medical research center , qubec , canada . surgeries were scheduled for total ( n = 184 ) or subtotal ( n = 6 ) abdominal hysterectomies sometimes accompanied by a salpingo - oophorectomy of one ( n = 27 ) or two ( n = 71 ) ovaries . reasons for surgery included one or more of the following : myoma ( n = 90 ) , menorrhagia / menometrorrhagia ( n = 83 ) , endometriosis ( n = 30 ) , fibroids ( n = 29 ) , benign cyst ( n = 28 ) , incapacitating dysmenorrhea ( n = 18 ) , pelvic pain ( n = 11 ) , endometrial hyperplasia ( n = 8) , polyp ( n = 7 ) , pelvic adhesions ( n = 5 ) , adenomyosis ( n = 3 ) , severe premenstrual syndrome ( n = 2 ) , and/or ovarian thecoma ( n = 1 ) . menopausal status determination was based on follicle - stimulating hormone levels , menstrual history questionnaires , and medical files . thirty - three women were identified as postmenopausal , whereas the remaining women were identified as pre- or peri - menopausal ( n = 157 ) . severely obese women ( n = 17 ) undergoing biliopancreatic diversion were recruited at the laval university cardiology and pulmonology institute . they were aged 47 years on average , and their bmi ranged from 39.9 to 70.5 kg / m . severe obesity was defined using the bmi cutoff of the world health organization ( who ) ( 40 kg / m ) . written informed consent the project was approved by the ethics committees of laval university cardiology and pulmonology institute and laval university medical research center . within a few days before or after the surgery , measurements of total adiposity and body fat distribution were performed in most women ( n = 150 ) . classification of normal weight , overweight , and obese women was performed using bmi cutoff points of who . total body fat mass and lean body mass were determined using dual - energy x - ray absorptiometry . abdominal subcutaneous and visceral adipose tissue cross - sectional area measures were obtained at the l4-l5 vertebrae level using a light speed 1.1 ct scanner ( general electric medical systems , milwaukee , wi ) ( 20,21 ) . plasma vldl were isolated by ultracentrifugation , and the hdl fraction was obtained after precipitation of ldl in the infranatant with heparin and mncl2 . the hdl2 and hdl3 subfractions were obtained after further precipitation of hdl2 with dextran sulfate . cholesterol and triglyceride levels were measured in plasma and lipoprotein fractions by enzymatic methods with a technicon ra-500 analyzer ( bayer , etobicoke , canada ) as previously described ( 22 ) . apolipoprotein ( apo ) b concentrations were measured in plasma , vldl , or ldl fractions by the rocket immunoelectrophoretic method of laurell ( 20 ) . glucose was measured using the glucose oxidase method and insulin was quantified by radioimmunoassay ( linco research , st . the homeostasis model assessment of insulin resistance ( homa - ir ) index was calculated using the following formula : fasting insulin ( in u / ml )  fasting glucose ( in mmol / l )  22.5 ( 23 ) . none of the women recruited from the gynecology unit had a previous diagnosis of diabetes or took antidiabetic drugs . however , monitoring fasting plasma glycemia on the morning of surgery revealed that 30 women had impaired fasting glycemia ( > 6.1 mmol / l ) . within 15 min after the beginning of the surgical procedure , paired samples of subcutaneous and omental adipose tissue were respectively collected at the site of surgical incision and the greater omentum . a portion of the tissue sample was digested 45 min at 37c in krebs - ringer - henseleit buffer supplemented with 350 units / ml of type 1 collagenase according to a modified version of the rodbell method ( 21,24 ) . mature adipocyte suspensions were then washed three times using krebs - ringer - henseleit buffer . mean adipocyte diameter for each adipose tissue sample was calculated from 250 individual measurements using scion image software ( frederick , md ) . sd and skewness of adipocyte size distributions were not independently associated to metabolic alterations and were not included in subsequent analyses . the number of subcutaneous and visceral adipocytes at the l4-l5 vertebrae level was estimated by dividing abdominal subcutaneous and visceral adipose tissue area , respectively , by subcutaneous and omental mean cross - sectional adipocyte surface . nonlinear curve fit of the association between subcutaneous or omental adipocyte size and bmi was performed using a one - phase exponential equation in prism graphpad software . an independent linear regression analysis was performed to predict adipocyte size in each compartment separately using measures of body composition ( bmi , fat mass , and lean body mass ) and fat distribution ( total , subcutaneous , and visceral adipose tissue area at l4-l5 vertebrae ) as well as age , menopausal status , and hormone replacement therapy . in models with models were first selected based on the mallows ' cp statistic and further improved using the adjusted r and the predicted residual sum of squares ( press ) . for each model , the study sample was stratified in two subgroups according to whether women had a positive ( hypertrophy ) or negative ( hyperplasia ) residual . in each fat depot model , adiposity and metabolic measures between subgroups variables that were not normally distributed based on a significant shapiro - wilk test ( p < 0.05 ) were log10- or box - cox - transformed . two subgroups of 54 women matched for visceral adipose tissue area and subcutaneous adipocyte size but with either small or large omental adipocytes were selected . adiposity and metabolic measures between women characterized by small or large omental adipocytes were compared using paired t tests . multivariate logistic regression analyses were performed to predict the probability of being characterized by hypertriglyceridemia ( > 1.69 mmol / l ) using measures of adipocyte size and number in each adipose tissue depot . the model was adjusted for body composition and fat distribution variables as well as age and menopausal status . odds ratios ( ors ) for each independent variable were computed for a 10% increase . the main study sample included 190 women aged 33 to 68 years recruited through the elective surgery schedule of the gynecology unit at the laval university medical research center , qubec , canada . surgeries were scheduled for total ( n = 184 ) or subtotal ( n = 6 ) abdominal hysterectomies sometimes accompanied by a salpingo - oophorectomy of one ( n = 27 ) or two ( n = 71 ) ovaries . reasons for surgery included one or more of the following : myoma ( n = 90 ) , menorrhagia / menometrorrhagia ( n = 83 ) , endometriosis ( n = 30 ) , fibroids ( n = 29 ) , benign cyst ( n = 28 ) , incapacitating dysmenorrhea ( n = 18 ) , pelvic pain ( n = 11 ) , endometrial hyperplasia ( n = 8) , polyp ( n = 7 ) , pelvic adhesions ( n = 5 ) , adenomyosis ( n = 3 ) , severe premenstrual syndrome ( n = 2 ) , and/or ovarian thecoma ( n = 1 ) . menopausal status determination was based on follicle - stimulating hormone levels , menstrual history questionnaires , and medical files . thirty - three women were identified as postmenopausal , whereas the remaining women were identified as pre- or peri - menopausal ( n = 157 ) . severely obese women ( n = 17 ) undergoing biliopancreatic diversion were recruited at the laval university cardiology and pulmonology institute . they were aged 47 years on average , and their bmi ranged from 39.9 to 70.5 kg / m . severe obesity was defined using the bmi cutoff of the world health organization ( who ) ( 40 kg / m ) . written informed consent the project was approved by the ethics committees of laval university cardiology and pulmonology institute and laval university medical research center . within a few days before or after the surgery , measurements of total adiposity and body fat distribution were performed in most women ( n = 150 ) . classification of normal weight , overweight , and obese women was performed using bmi cutoff points of who . total body fat mass and lean body mass were determined using dual - energy x - ray absorptiometry . abdominal subcutaneous and visceral adipose tissue cross - sectional area measures were obtained at the l4-l5 vertebrae level using a light speed 1.1 ct scanner ( general electric medical systems , milwaukee , wi ) ( 20,21 ) . plasma vldl were isolated by ultracentrifugation , and the hdl fraction was obtained after precipitation of ldl in the infranatant with heparin and mncl2 . the hdl2 and hdl3 subfractions were obtained after further precipitation of hdl2 with dextran sulfate . cholesterol and triglyceride levels were measured in plasma and lipoprotein fractions by enzymatic methods with a technicon ra-500 analyzer ( bayer , etobicoke , canada ) as previously described ( 22 ) . apolipoprotein ( apo ) b concentrations were measured in plasma , vldl , or ldl fractions by the rocket immunoelectrophoretic method of laurell ( 20 ) . glucose was measured using the glucose oxidase method and insulin was quantified by radioimmunoassay ( linco research , st . the homeostasis model assessment of insulin resistance ( homa - ir ) index was calculated using the following formula : fasting insulin ( in u / ml )  fasting glucose ( in mmol / l )  22.5 ( 23 ) . none of the women recruited from the gynecology unit had a previous diagnosis of diabetes or took antidiabetic drugs . however , monitoring fasting plasma glycemia on the morning of surgery revealed that 30 women had impaired fasting glycemia ( > 6.1 mmol / l ) . within 15 min after the beginning of the surgical procedure , paired samples of subcutaneous and omental adipose tissue were respectively collected at the site of surgical incision and the greater omentum . a portion of the tissue sample was digested 45 min at 37c in krebs - ringer - henseleit buffer supplemented with 350 units / ml of type 1 collagenase according to a modified version of the rodbell method ( 21,24 ) . mature adipocyte suspensions were then washed three times using krebs - ringer - henseleit buffer . mean adipocyte diameter for each adipose tissue sample was calculated from 250 individual measurements using scion image software ( frederick , md ) . sd and skewness of adipocyte size distributions were not independently associated to metabolic alterations and were not included in subsequent analyses . the number of subcutaneous and visceral adipocytes at the l4-l5 vertebrae level was estimated by dividing abdominal subcutaneous and visceral adipose tissue area , respectively , by subcutaneous and omental mean cross - sectional adipocyte surface . nonlinear curve fit of the association between subcutaneous or omental adipocyte size and bmi was performed using a one - phase exponential equation in prism graphpad software . an independent linear regression analysis was performed to predict adipocyte size in each compartment separately using measures of body composition ( bmi , fat mass , and lean body mass ) and fat distribution ( total , subcutaneous , and visceral adipose tissue area at l4-l5 vertebrae ) as well as age , menopausal status , and hormone replacement therapy . in models with models were first selected based on the mallows ' cp statistic and further improved using the adjusted r and the predicted residual sum of squares ( press ) . for each model , the study sample was stratified in two subgroups according to whether women had a positive ( hypertrophy ) or negative ( hyperplasia ) residual . in each fat depot model , adiposity and metabolic measures between subgroups variables that were not normally distributed based on a significant shapiro - wilk test ( p < 0.05 ) were log10- or box - cox - transformed . two subgroups of 54 women matched for visceral adipose tissue area and subcutaneous adipocyte size but with either small or large omental adipocytes were selected . adiposity and metabolic measures between women characterized by small or large omental adipocytes were compared using paired t tests . multivariate logistic regression analyses were performed to predict the probability of being characterized by hypertriglyceridemia ( > 1.69 mmol / l ) using measures of adipocyte size and number in each adipose tissue depot . the model was adjusted for body composition and fat distribution variables as well as age and menopausal status . odds ratios ( ors ) for each independent variable were computed for a 10% increase . subcutaneous and omental adipocyte size was measured in a sample of 207 lean to severely obese women . the curve - linear relationship between bmi and adipocyte size in each depot adipocyte size increased along with bmi and tended to reach a plateau at 130 m in severely obese women . taken as a whole , omental adipocytes were smaller than subcutaneous adipocytes but tended to reach similar sizes in severely obese women ( bmi > 40 kg / m ) . subsequent analyses were performed in lean to moderately obese women undergoing gynecological surgery , since the relation between adipocyte size and adiposity became nonlinear in severely obese women . subcutaneous and omental adipocyte diameter according to bmi in women undergoing abdominal gynecologic surgery ( n = 190 ) and biliopancreatic diversion ( n = 17 ) . women were aged 47.7  5.5 years ( range 3068.3 years ) with a mean bmi of 28.5  8.8 kg / m ( range 17.6 70.5 kg / m ) . mean subcutaneous and omental adipocyte sizes were 101.5  15.4 m and 85.2  18.6 m , respectively . associations between regional adipocyte size and lipid profile measures were computed in a subsample of women for which data on body composition , fat distribution , and lipid profile were available ( n = 150 ) . characteristics of these women are shown in table 1 . according to mean bmi and body composition measures , we performed linear regression models to predict subcutaneous and omental adipocyte sizes using all body composition and fat distribution variables available ( table 2 ) . based on this analysis , lean body mass as well as subcutaneous and visceral adipose tissue area explained 30.8% of the variance in subcutaneous adipocyte size ( model 1 ) . lean body mass , bmi , and visceral adipose tissue area explained 54.3% of the variance in omental adipocyte size ( model 2 ) . physical and metabolic characteristics of the subsample of 150 women linear regression analyses predicting omental and subcutaneous adipocyte size in women * regression models included bmi , body fat mass , lean body mass , subcutaneous adipose tissue area , visceral adipose tissue area , age , menopausal status , and hormone replacement therapy . models were selected based on the mallows cp , adjusted r , and press statistics ; colinearity among independent variables was assessed through inflation and condition index statistics . a large percentage of the variance in adipocyte size remained unexplained despite considering body composition and fat distribution measures . to assess the impact of adipocyte size variation on the metabolic profile independent of body composition and fat distribution , we stratified the study sample according to the difference between measured and predicted adipocyte size in each model . women with larger adipocytes than predicted by the regression model ( positive residual ) were identified as hypertrophic , whereas women with smaller adipocytes than predicted by the model were identified as hyperplasic ( negative residual ) in the corresponding adipose tissue compartment . by design , stratifications performed using each model generated subgroups of women characterized by identical body composition and fat distribution values . figure 2 shows adipocyte size and number in each adipose tissue compartment according to the presence of hypertrophy or hyperplasia in subcutaneous ( left ) or omental ( right ) adipose tissue . women characterized by hypertrophic subcutaneous adipocytes had fewer but larger subcutaneous adipocytes than women with hyperplasic subcutaneous adipocytes ( p < 0.0001 ) . women characterized by subcutaneous adipocyte hypertrophy also had slightly larger omental adipocytes , but their cell number remained similar to that of women characterized by subcutaneous adipocyte hyperplasia ( p < 0.05 ) . similarly , larger but fewer omental adipocytes were observed in women characterized by omental adipocyte hypertrophy compared with women characterized by omental adipocyte hyperplasia ( p < 0.0001 ) . although the number of subcutaneous adipocytes was similar in both groups derived from model 2 , slightly larger subcutaneous adipocytes were observed in women characterized by omental adipocyte hypertrophy ( p < 0.05 ) . adipocyte diameter ( a ) and adipocyte number at the l4-l5 vertebrae level ( b ) are shown for subcutaneous ( sc ; model 1 ; n = 150 ) and omental ( om ; model 2 ; n = 150 ) adipose tissue cellularity stratifications . values are mean  sem . * p < 0.05 ; * * p < 0.01 . no significant difference in blood lipids was observed between women characterized by subcutaneous adipocyte hypertrophy versus subcutaneous adipocyte hyperplasia ( fig . women characterized by omental adipocyte hypertrophy had higher levels of plasma triglycerides , higher vldl triglycerides , and higher vldl cholesterol levels compared with women characterized by omental adipocyte hyperplasia ( fig . the ratio of total cholesterol to hdl cholesterol was significantly higher in women characterized by omental adipocyte hypertrophy compared with women characterized by omental adipocyte hyperplasia ( fig . 3d , right ) . increased triglyceride and cholesterol content in the vldl fraction may suggest increased particle size ( 10.89  3.85 vs. 9.27  3.97 mmol of lipids / g of apob , p < 0.01 ) rather than increased particle number as estimated by vldl - apob ( 0.13  0.06 vs. 0.12  0.07 g / l , ns ) . lipid profile in women characterized by hypertrophic or hyperplasic subcutaneous ( model 1 ; n = 150 ) and omental ( model 2 ; n = 150 ) adipocytes . overnight fast values of plasma triglyceride ( a ) ( mmol / l ) , vldl triglyceride ( b ) ( mmol / l ) , vldl cholesterol ( c ) ( mmol / l ) , and total - to - hdl cholesterol ( d ) are shown . subdivision of women in three subgroups according to the sd of the linear regression model residuals generated results that are comparable with the two - group analyses . specifically , women with adipocyte sizes inside of 1 sd around the mean showed an intermediate phenotype for blood lipid levels compared with women above or below 1 sd of the regression residuals ( data not shown ) . no significant difference was observed in fasting glucose ( 5.75  0.65 vs. 5.60  0.59 , ns ) and insulin levels ( 10.15  5.93 vs. 8.88  5.05 , ns ) as well as in homa - ir index ( 2.68  1.71 vs. 2.34  1.60 , ns ) among women characterized by omental adipocyte hypertrophy or hyperplasia . however , when the linear regression analyses were performed using a single measure of total adiposity ( i.e. , fat mass ) to predict adipocyte size , we observed a trend for higher fasting glucose ( 5.75  0.64 vs. 5.57  0.59 , p = 0.09 ) , significantly higher fasting insulin levels ( 10.9  6.3 vs. 7.8  3.8 , p < 0.005 ) , as well as a higher homa - ir index ( 2 . < 0.001 ) in women characterized by subcutaneous adipocyte hypertrophy compared with women characterized by subcutaneous adipocyte hyperplasia . to confirm results of the regression analyses , subgroups of women matched for fat mass , visceral adipose tissue area , and subcutaneous adipocyte size but with either small or large omental adipocytes were compared ( table 3 ) . by design , both subgroups had a similar body composition and fat distribution . although subcutaneous adipocyte size and number were comparable , women with large omental adipocytes had a lower number of visceral adipocytes . women with large omental adipocytes had higher levels of plasma triglycerides , of vldl triglycerides , and of vldl cholesterol . a trend for lower hdl cholesterol the lower hdl cholesterol value was explained by significantly lower cholesterol content in hdl2 , but not in hdl3 lipoproteins , in women with larger omental adipocytes . moreover , the total cholesterol - to - hdl - cholesterol ratio tended to be higher in women with large omental adipocytes compared with women with small omental adipocytes . fasting glucose and insulin concentrations as well as the homa - ir index were similar between women with large versus small omental adipocytes ( table 3 ) . characteristics of women matched for visceral adipose tissue area and subcutaneous adipocyte size but with either small or large omental adipocytes ( n = 54 ) the risk of hypertriglyceridemia , defined by triglyceride levels greater than 1.69 mmol / l in women , was assessed using logistic regression analyses ( table 4 ) . when adipocyte size and number in each fat depot were included in the model , the risk of hypertriglyceridemia was associated with adipose tissue cellularity measures of the visceral , but not the subcutaneous , fat compartment . indeed , the risk of hypertriglyceridemia was significantly higher in women with 10% larger omental adipocytes ( or 2.08 [ 95% ci 1.483.04 ] ) and with 10% more adipocytes in visceral adipose tissue ( or 1.16 [ 1.031.30 ] ) . after adjustment for bmi , body fat mass , lean body mass , subcutaneous adipose tissue area , visceral adipose tissue area , age , and menopausal status , omental adipocyte size ( adjusted or 4.06 [ 1.929.97 ] ) and number ( adjusted or 1.55 [ 1.122.29 ] ) remained independent predictors of hypertriglyceridemia in women . mmol / l * logistic regression model was adjusted for body fat mass ( ns ) , subcutaneous adipose tissue area ( ns ) , visceral adipose tissue area ( p = 0.07 ) , free fat mass ( ns ) , bmi ( ns ) , age ( ns ) , menopausal status ( ns ) , and hormone replacement therapy ( ns ) ; n = 150 . we designed this study to assess whether subcutaneous and omental adipose tissue cellularity measures were related to metabolic alterations independent of body composition and fat distribution in women . using linear regression analyses , women were subdivided in two groups having lower - than - predicted ( hyperplasia ) or higher - than - predicted ( hypertrophy ) adipocyte sizes in subcutaneous and omental adipose tissue . women characterized by omental adipocyte hypertrophy presented a deleterious lipid profile compared with women characterized by omental adipocyte hyperplasia . these alterations in the lipid profile were , by design , independent of differences in body composition and fat distribution . in contrast , lipid profiles were similar in women characterized by subcutaneous adipocyte hypertrophy versus subcutaneous adipocyte hyperplasia . in logistic regression analyses including body composition and fat distribution measures , we estimated that a 10% enlargement of omental adipocytes increased the risk of hypertriglyceridemia by more than fourfold , whereas enlarged subcutaneous adipocyte size failed to significantly alter the risk of hypertriglyceridemia in women . to a lower extent , a 10% increase in the number of visceral , but not subcutaneous , adipocytes multiplied the risk of hypertriglyceridemia in women by 1.55-fold . these results suggest that omental fat cell size and number predict lipid profile alterations independent of body composition and fat distribution in women . despite the fact that total and visceral adiposity are known modulators of the lipid profile , we show here for the first time that the extent of omental adipocyte hypertrophy may influence this relation . previous studies reported that subcutaneous adipocyte hypertrophy was associated with alterations in glucose homeostasis ( 1,5,911 ) . ( 1 ) on adipocyte hypertrophy and adipocyte turnover showed that individuals characterized by larger subcutaneous adipocytes had higher fasting insulin levels and homa - ir index . in the current study , all measures of body composition and fat distribution as well as age and menopausal status were used to prepare fully adjusted predictive models for subcutaneous and omental adipocyte size . using these models , we failed to observe alterations in glucose homeostasis measures in women characterized by adipocyte hypertrophy in subcutaneous or omental adipose tissue . on the other hand , linear regression analyses predicting adipocyte size performed using only one measure of total adiposity ( e.g. , fat mass ) revealed glucose homeostasis alterations in women characterized by subcutaneous adipocyte hypertrophy compared with women characterized by subcutaneous adipocyte hyperplasia . these results suggest that associations of glucose homeostasis with subcutaneous adipocyte hypertrophy , as observed by others ( 1,5,911 ) , may arise from differences in abdominal fat distribution rather than differences in subcutaneous adipose tissue cellularity . lack of statistical adjustment for fat distribution measures in previous studies may explain discrepancies regarding glucose homeostasis alterations in women characterized by hypertrophic subcutaneous adipocytes ( 1,5,911 ) . to our knowledge , we are the first to report an independent association between omental adipocyte hypertrophy and alterations of the lipid profile in women . with the exception of two studies ( 10,19 ) , most authors assessed the association between adipocyte size and metabolic parameters using only measures from subcutaneous adipose tissue ( 1,3,5,11 ) . these studies reported that enlarged subcutaneous adipocytes were associated with insulin resistance independent of obesity itself ( 1,5,11 ) . in contrast , mundi et al . ( 3 ) observed that insulin and triglyceride levels were slightly better predicted by body composition measures than subcutaneous adipocyte size . therefore , they dismissed the individual effect of subcutaneous adipocyte size on metabolic parameters in men and women ( 3 ) . subcutaneous and omental adipocyte size measures are closely related ( 4,25 ) , and part of the effect of omental adipocyte hypertrophy may be indirectly related to subcutaneous adipocyte size . however , lack of visceral adipocyte size measures in most of these studies may explain discrepancies observed between our analysis and previous literature ( 1,3,5 ) . we corroborate reports showing that body composition and fat distribution measures largely predict subcutaneous and omental adipocyte size ( 4 ) . however , after adjustment for all anthropometric measures available , interindividual variability observed in subcutaneous and omental adipose tissue was not completely explained . this observation is consistent with the hypothesis that adipocyte size is regulated by factors that are independent of variations in body composition and fat distribution ( 4 ) . bergman et al . ( 26 ) suggested that fat accumulation occurs primarily in the visceral adipose tissue depot and fat storage then spills over in the subcutaneous adipose tissue depot , whereas others have proposed that subcutaneous fat is a primary compartment ( 27,28 ) . in any case , lipid uptake and lipolysis rates in each fat depot appear as dynamic processes . ( 2 ) observed that hyperplasia is predominant in the subcutaneous adipose tissue , whereas adipocyte hypertrophy is present in both adipose tissue depots . because less than 10% of mature adipocytes are renewed each year in subcutaneous adipose tissue ( 29 ) , cell hyperplasia may represent a long - term adipose tissue adaptation to face excess energy intake . conversely , the predominance of cell hypertrophy in visceral adipose tissue may suggest that it is a short - term storage compartment . activated receptor- agonist  induced hyperplasia has been shown to promote fat redistribution and to reduce visceral fat accumulation ( 30 ) . these observations show that increasing adipogenic capacity in subcutaneous adipose tissue may attenuate visceral adipocyte hypertrophy and related alterations . although this study was not designed to investigate the mechanisms involved in the association of adipocyte hypertrophy and metabolic alterations , several hypotheses may be put forward . involvement of visceral , but not subcutaneous , adipose tissue cellularity could indirectly reinforce the role of excess free fatty acids ( 31 ) . indeed , previous studies have reported that large adipocytes showed alterations in lipolysis , insulin sensitivity , and adipokine secretion compared with smaller adipocytes from the same individual ( 12,13,15,16 ) . although visceral adipose tissue is not believed to be a major source for the circulating free fatty acid pool , the contribution of visceral adipose tissue lipolysis to hepatic free fatty acid delivery is positively associated to visceral fat accumulation ( 32 ) . increased responsiveness to -adrenergic agonist stimulation ( 3335 ) and decreased sensitivity to insulin suppression of lipolysis ( 36,37 ) in hypertrophic omental adipocytes could possibly impact splanchnic free fatty acid levels , especially in the visceral obese . increased free fatty acid delivery to the liver was suggested to increased triglyceride - rich vldl production , which is associated with small , dense ldl particles as well as with lower hdl cholesterol levels ( 38,39 ) . the altered lipid profile observed in women characterized by omental adipocyte hypertrophy is , therefore , consistent with this hypothesis . an altered adipokine secretion pattern , as observed with large adipocytes , may also influence local adipose tissue lipid metabolism and generate abnormal adipose - derived signaling through the portal vein ( 15 ) . moreover , reduced cellular stability of large adipocytes may increase the risk of cell rupture in hypertrophic adipose tissue ( 40 ) . chronic , low - grade inflammation provoked by adipocyte death may then contribute to the metabolic alterations associated with obesity ( 41 ) . results of this study are strengthened by the use of extensive measures of adiposity and body fat distribution together with characterization of subcutaneous and omental adipose tissue cellularity . moreover , the absence of differences in body composition and fat distribution measures between women characterized by hypertrophy and hyperplasia supports the validity and the strength of the methodology used . we suggest that this stratification is adequate to assess metabolic alterations associated to subcutaneous or omental hypertrophy , independent of body composition and fat distribution . however , some limitations in the study design should be acknowledged . the present analyses are based on cross - sectional data , and it is hazardous to conclude cause - and - effect relationships between visceral adipocyte hypertrophy and the development of metabolic alterations in women . the difficulty to recruit lean to moderately obese men undergoing abdominal surgery limits our capacity to perform a comparable study in men . most previous studies ( 1,3,5,9 ) included both men and women , but only subcutaneous adipose tissue cellularity was assessed . this study was not designed to assess the involvement of very small adipocytes in metabolic alterations since we used collagenase - digested adipose tissue samples . ( 42 ) suggesting that the proportion of very small adipocytes is associated with metabolic alterations . finally , because we only had access to omental and not mesenteric adipose tissue , visceral adipocyte numbers were computed using omental adipocyte surface . we assumed that mean adipocyte sizes in each visceral adipose tissue depot are strongly correlated , as previously observed for the subcutaneous and visceral adipose tissue depots ( 4 ) . during the revision process of this article , hoffstedt et al . ( 43 ) published a similar study reporting that visceral adipose tissue hypertrophy is associated with dyslipidemia . the recruitment of morbidly obese women and our use of detailed assessment of body fat distribution may account for these discrepancies . in conclusion , our results support the hypothesis that omental adipose tissue cellularity is an important predictor of hypertriglyceridemia in women . we demonstrate that the association between omental adipocyte hypertrophy and lipid profile alterations is independent of differences in subcutaneous adipose tissue cellularity , body composition , and fat distribution in women .