Omental adipocyte hypertrophy relates to coenzyme Q10 redox state and lipid peroxidation in obese women.

Occurrence of oxidative stress in white adipose tissues contributes to its dysfunction and the development of obesity-related metabolic complications. Coenzyme Q10 (CoQ10) is the single lipophilic antioxidant synthesized in humans and is essential for electron transport during mitochondrial respiration. To understand the role of CoQ10 in adipose tissue physiology and dysfunction, the abundance of the oxidized and reduced (CoQ10red) isoforms of the CoQ10 were quantified in subcutaneous and omental adipose tissues of women covering the full range of BMI (from 21.5 to 53.2 kg/m(2)). Lean women displayed regional variations of CoQ10 redox state between the omental and subcutaneous depot, despite similar total content. Obese women had reduced CoQ10red concentrations in the omental depot, leading to increased CoQ10 redox state and higher levels of lipid hydroperoxide. Women with low omental CoQ10 content had greater visceral and subcutaneous adiposity, increased omental adipocyte diameter, and higher circulating interleukin-6 and C-reactive protein levels and were more insulin resistant. The associations between abdominal obesity-related cardiometabolic risk factors and CoQ10 content in the omental depot were abolished after adjustment for omental adipocyte diameter. This study shows that hypertrophic remodeling of visceral fat closely relates to depletion of CoQ10, lipid peroxidation, and inflammation.

samples were immediately carried to the laboratory and used for adipocyte isolation. A portion of each sample was fl ash frozen in liquid nitrogen and stored at Ϫ 80°C.

Adipocyte isolation and cell sizing
Tissue samples were digested with collagenase type I in Krebs-Ringer-Henseleit buffer for 45 min at 37°C according to a modifi ed version of the Rodbell method (14)(15)(16). Cell suspensions were fi ltered through nylon mesh and washed three times with Krebs-Ringer-Henseleit buffer. To determine adipocyte diameter, pictures of 250 cells were taken with a phase contrast microscope and analyzed with Scion Image software. The collagenase digestion was not performed for three samples because of the limited amount of tissue.

Measurement of body composition and adipose tissue distribution
The determination of body fat and lean body mass was performed by dual-energy X-ray absorptiometry (DEXA) using a Hologic QDR-2000 densitometer and the enhanced array whole-body software V5.73A (Hologic, Bedford, MA). Regional adipose tissue distribution was measured by computed tomography (CT) as previously described ( 14,17 ) using a GE Light Speed 1.1 CT scanner (General Electric Medical Systems, Milwaukee, WI). Briefl y, the cross-sectional scan was performed at the L4-L5 vertebrae level in supine position with arms over the head. The exact scanning position was determined using a scout image. Adipose tissue areas of interest including visceral and subcutaneous adipose tissue areas, the latter included superfi cial and deep subcutaneous adipose tissues, were highlighted and computed with attenuation ranging from Ϫ 190 to Ϫ 30 Hounsfi eld units with ImageJ 1.33u software (National Institutes of Health, Bethesda, MD). Two obese volunteers exceeded the CT scanner fi eld of view, and only the visceral adipose tissue area was determined. One of these women also exceeded the upper limit of weight allowed for the DEXA table and did not undergo this test.

Quantifi cation of lipid hydroperoxide levels in white adipose tissues
Lipid hydroperoxides (LPOs) were quantifi ed using an LPO assay kit purchased from Cayman Chemical (Ann Arbor, MI), performed according to supplier recommendations with minor modifi cations. Briefl y, 50 mg of omentum and subcutaneous adipose tissues were homogenized in methanol. Lipid extraction was achieved by adding 500 µl of water and 1 ml of chloroform. The mixture was centrifuged at 1,500 g , and the organic phase was collected. An aliquot was used to perform the colorimetric reaction, and absorbance was read at 500 nm with a 96-well plate reader.

Quantifi cation of CoQ10 isoforms
The quantifi cation of both isoforms was performed by reversephase HPLC with electrochemical detection as previously described ( 18 ). The HPLC-EC system is composed of a Gilson 307 pump, a Rheodine injector, an analytical column, and an ESA Coulochem 2 Electrochemical Detector (Model 5200 A) with a computer/controller with EuroChrom 2000 Integration Package. The analytical cell (ESA Model 5010 porous graphite) consisted of a series of two coulometric electrodes and was connected in series to the analytical column: the fi rst electrode (E2) was for reduction of CoQs, and the second electrode (E3) was for detection of these reduced CoQs. The identifi cation of the different forms was set by the chromatographic separation with an analytical column, a reverse-phase Hypersil BDS C18 column (4 mm × 25 cm, 5 µm bead). The mobile phase for the isocratic elution of internal standard from ChromSystem and CoQ10s containing condensation of the isoprenyl side chain with the benzoquinone nucleus is catalyzed by the coenzyme Q2 4hydroxybenzoate polyprenyltransferase (COQ2) enzyme ( 8 ). This is the cellular compartment with the highest concentration, where it shuttles electrons from complexes I and II to complex III during oxidative phosphorylation ( 7,9 ). Moreover, CoQ10 has been shown to modulate the activity of uncoupling protein ( 9 ). CoQ10 was also found in the Golgi apparatus, the endoplasmic reticulum, and plasma membrane ( 10 ). The extra mitochondrial CoQ10 pool is involved in plasma membrane electron transport catalyzed by NAD(P)H-dependent enzymes ( 11 ). Moreover, the reduced isoform displays direct or indirect antioxidant properties by scavenging lipid peroxyl radical or by reducing ␣ -tocophenol ( 12 ).
Depletion of CoQ10 content was found in subcutaneous adipose tissue of obese subjects and mice ( 13 ). Overexpression of COQ2 in 3T3-F442A preadipocytes decreased the CoQ redox state and promoted ROS synthesis by the mitochondria ( 13 ). Interestingly, the adipogenic potential of these cells was almost completely blunted, suggesting an important role of CoQ content and redox state during adipogenesis and adipose tissue expansion. However, the variation in CoQ10 content and redox state in subcutaneous and omental adipose tissues has not been investigated in humans. Moreover, the potential contribution of these parameters to white adipose tissue dysfunction and obesity-related metabolic complications remains unclear.
In the present study, we have explored physiological variations in CoQ10 content and redox state in omental and subcutaneous adipose tissue of lean, overweight, and obese women. We hypothesized that CoQ10 red content is lower in omental fat of obese individuals and is associated with lipid peroxidation. The loss of lipophilic antioxidant capacity of this molecule could be an important mechanism. We also postulate that this phenomenon could link visceral adipose tissue hypertrophy to systemic low-grade infl ammation and insulin resistance.

Adipose tissue sampling
Subcutaneous adipose tissue samples were collected at site of the surgical incision (lower abdomen), while omental samples were removed from the distal part of the greater omentum. Fresh were selected from a previous publication ( 13 ). Differences between women with low and high concentrations of CoQ10 were analyzed by Student's t -test or Mann-Whitney test. Multiple univariate Pearson's linear correlations were performed to fi nd associations between adiposity measurements and the concentrations of the CoQ10 isoforms for both depots. Log10 and Box-Cox transformations were used for correlations with nonnormally distributed residuals. Statistically signifi cant correlations (in omental depot) between body fat distribution parameters and CoQ10 isoforms were adjusted for omental fat cell diameter to investigate the confounding effect of visceral fat hypertrophy. Statistical analyses were performed with the JMP 11.0 (SAS Institute, Cary, NC) and Graph-Pad Prism 6 (GraphPad, a Jolla, CA) software.

Volunteer characteristics
Twenty-nine Caucasian women aged between 40.4 and 55.5 years (mean of 48.1 ± 4.1) were recruited. Their anthropometric and metabolic characteristics are shown in Table 1 . They were characterized by a wide range of BMI values (from 21.5 to 51.3 kg/m 2 ) with an average around the class I obesity threshold (30.0 ± 6.8 kg/m 2 ). Of the 29 volunteers, 7 were lean (BMI <25.0 kg/m 2 ), 12 were overweight (BMI 25.0 kg/m 2 to 30.0 kg/m 2 ), and 10 were obese (BMI >30.0 kg/m 2 ). Twelve of the 29 subjects were insulin resistant based on a HOMA-IR value >2.5, but none of them had type 2 diabetes. This sample was specifi cally sodium acetate, acetic acid and 2-propanol, methanol and hexane, suited for EC detector. The standards of CoQ10 ox were obtained from Sigma. Identifi cation and quantifi cation of oxidized and reduced forms of CoQs were performed using in-house external standards. The concentration of the working solution was confi rmed by measuring absorbance at a wavelength of 275 nm and by reference to known coeffi cients (E 1% 1cm 185 for CoQ9 and 165 for CoQ10). Then the conditioned solution of oxidized standard was reduced in loop to Ϫ 1,000 mV in the system pump-guard cell. The determination of the concentration of each form was compared with the QA program organized by the National Institute of Standard Technology on lyophilized serums. Calibration curves were performed with a mix of three different diluted working CoQ10s stock solutions. Before injection, each standard solution was prepared as the biological samples in propanol. A highly linear relationship was observed between the area of the peak (mV/min) and the molecular concentration ratios of each compound over a wide concentration from 10-15 nM to 3,000 nM ( r = 0.99). Acceptable repeatability was obtained for CoQs with a coeffi cient of variation below 5%, respectively 3.5% and 3.7% for CoQ10 red and CoQ10 ox . The limits of detection per injected quantity were 21 pmol for CoQ red and 15 pmol for CoQ ox .
To perform CoQ10 extraction, frozen tissues (100 mg) were added to 0.9 ml of 2-propanol and homogenized with an Ultraturax blender. One hundred microliters of this homogenate was mixed with 500 µl of 2-propanol during 30 s and then centrifuged (10,000 rpm for 3 min). Fifty microliters of the supernatant was directly injected in the system. This extraction procedure with only propanol was chosen because it was simple to perform and avoid oxidation of reduced CoQ forms as it was demonstrated and validated using various molecules well known to modify electron fl ow at different levels of the respiratory chain. As expected, CoQ redox state was signifi cantly decreased in the presence of antimycin A and signifi cantly increased in the presence of rotenone and carbonyl cyanide m -chlorophenyl hydrazine. The details of the validation were reported by Galinier et al. ( 18 ). The total coenzyme Q10 (CoQ10 tot ) pool was described as the sum of CoQ10 ox and CoQ10 red concentrations. Results were expressed as nmol/g of tissue. The redox state was calculated as follows: [CoQ10 ox ]/[CoQ10 tot ] × 100.

Estimation of daily dietary CoQ10 consumption
Dietary intake was assessed using a food frequency questionnaire validated by Goulet et al. ( 19 ) that was interviewer administered by the same investigator within 2 weeks preceding or following the surgery and was structured to represent food habits throughout the previous month. The questionnaire was based on foods available in the Quebec City area and refl ected Canadian food habits. The participants were questioned about the quantity and frequency intake of each item among different food groups: vegetables, fruits, legumes, nuts and seeds, cereals and grain products, milk and dairy products, meat/processed meat, poultry, fi sh, eggs, sweets, oil and fats, fast foods, and drinks. The content in CoQ10 by portion of each food groups was estimated using the compiled by Pravst et al. ( 20 ) and is reported in supplementary Fig. 1. Total daily consumption of CoQ10 was calculated as the sum from each food source.

Statistical analyses
All tables show mean ± standard error of the mean. Each graph shows dots as a single observation and horizontal lines as the mean of the distribution. Differences among body weight categories and adipose tissue depots were analyzed by two-way ANOVA, followed by Tukey's post hoc test. The stratifi cation of CoQ10 content in the omental and subcutaneous depot was performed using a cutoff value of 14.0 and 15.0 nmol/g of tissue, respectively. These values HOMA-IR , homeostasis model assessment-insulin resistance. a n = 28. b n = 27. levels quantifi cation as a marker of oxidative stress. The omental depot had higher levels of LPO than the subcutaneous compartment (depot effect: P < 0.0001; Fig. 2B ). We also observed a signifi cant increase in the omental LPO content of obese women compared with lean and overweight volunteers ( P = 0.01 and 0.02 respectively; Fig. 2B ).
A positive association was found between the CoQ10 redox state and LPO content in omental adipose tissue ( r = 0.67, P = 0.005; Fig. 2C ), supporting a role of the CoQ10 redox state in the regulation of redox status and oxidative stress in visceral fat. However, the association between CoQ10 tot and LPO levels was not statically signifi cant in this sample of patients ( r = Ϫ 0.41, P = 0.11). LPO concentration in subcutaneous adipose tissue was similar for all groups ( Fig. 2B ) and was not linked with the CoQ10 redox state (data not shown).
Infl uence of adipose tissue distribution and adipocyte diameter on CoQ10 content Table 2 provides the Pearson and Spearman Rho values describing the correlations between adipose tissue areas measured by axial tomography and the abundance of CoQ10 isoforms in subcutaneous and omental adipose tissues. We found signifi cant negative associations between designed to identify cardiometabolic risk factors and adipose tissue dysfunction, features that relate to obesity and fat distribution in women.

Dietary CoQ10 consumption and smoking status
Using a food frequency questionnaire, we found that women included in our study consumed an average of 4.6 mg of CoQ10 per day with a range from 2.0 to 8.0 mg/day. BMI of the volunteers did not infl uence their daily consumption of CoQ10 from diet (supplementary Fig. 1A). We also found that vegetal sources (oils, nuts, vegetables, and fruits) were the main sources of CoQ10 in this French Canadian population (supplementary Fig. 1C). In this study, CoQ10 consumption did not infl uence the total levels and redox state of this molecule in the omental (supplementary Fig. 2A-C) or the subcutaneous (supplementary Fig. 2 B-D) adipose tissue compartment. Only four volunteers were smokers and were distributed among BMI subgroups. We did not observe any specifi c pattern of CoQ10 content or redox state in adipose tissues of these individuals (data not shown).

Regional variation of CoQ10 in obesity
We were able to quantitatively assess the levels of CoQ10 ox and CoQ10 red in 24 omental and 22 subcutaneous samples. We excluded data from fi ve omental (overweight, n = 3; obese, n = 2) and seven subcutaneous (lean, n = 2; overweight, n = 4; obese, n = 1) samples because of complete oxidation of the CoQ10 red isoform during the extraction process. We considered the CoQ10 ox levels as the CoQ10 tot pool for these samples. However, only women with available data of CoQ10 ox , CoQ10 red , and CoQ10 tot within the same depot were included in this set of analysis. We fi rst analyzed the regional variation of CoQ10 content in lean, overweight, or obese patients. We did not observe a difference in CoQ10 tot content between the omental and subcutaneous adipose tissue of women within the same BMI category ( Fig. 1A ). However, we observed a depletion of the CoQ10 pool in omental adipose tissue of overweight and obese women, as well as in subcutaneous adipose tissue of obese women (BMI effect: P = 0.001; Fig. 1A ). In lean individuals, we measured higher concentrations of the CoQ10 red isoform in the omental depot compared with subcutaneous tissue ( P = 0.003; Fig. 1B ). However, we found higher levels of CoQ10 ox isoform in subcutaneous adipose tissue of these women ( P = 0.01; Fig. 1C ). As expected, they displayed greater CoQ10 redox state in the subcutaneous depot (depot effect: P = 0.0003; Fig. 2A ), suggesting that omental and subcutaneous adipose tissues have distinct CoQ10 redox statuses in healthy volunteers. The content in CoQ10 red was decreased specifi cally in omental adipose tissue of obese women ( P = 0.007; Fig. 1B ). A reduction in CoQ10 ox concentrations was also observed in subcutaneous adipose tissue of overweight and obese volunteers ( Fig. 1C ). Because of these differences, regional variations in CoQ10 redox state were not signifi cant ( Fig. 2A ).

CoQ10 redox state and oxidative stress in abdominal adipose tissues
For samples with valid CoQ10 redox state data, 16 omental and 18 subcutaneous fat samples were available for LPO The presence of the CoQ10 ox isoform in omentum was not associated with visceral or subcutaneous adiposity. The CoQ10 redox state of the visceral depot was also weakly associated with visceral adipose tissue area ( r = 0.37, P = 0.08) and deep subcutaneous adipose tissue area ( r = 0.39, P = 0.07). To test the hypothesis that visceral adipocyte hypertrophy is a major contributor to CoQ10 depletion in obesity, we adjusted the previous correlations for omental fat cell diameter. The association between omental CoQ10 red content and adipose tissue areas was no longer signifi cant. Adjustment also abolished the relationship between the CoQ10 tot pool and visceral adipose tissue area, although the correlation with subcutaneous adipose tissue areas remained statistically signifi cant ( r = Ϫ 0.40, P = 0.05).

Metabolic effects of low adipose tissue CoQ10 concentration
In a previous study, the concentration of 13.26 nmol of CoQ10 per gram of subcutaneous adipose tissue was identifi ed as a phenotypic threshold value below which 95% of volunteers are obese ( 13 ). To quantify the metabolic effect of low and high CoQ10 content, we used a cutoff value of 14.0 and 15.0 nmol/g of subcutaneous and omental adipose tissues. This stratifi cation generated two groups with either low or high CoQ10 tot concentrations within the same tissue ( Fig. 3A-C ). The women with low levels of CoQ10 in omental adipose tissue also displayed lower Co-Q10 red concentrations ( P < 0.01; Fig. 3A ). The amount of CoQ10 ox ( Fig. 3A ) and the redox state ( Fig. 3B ) were not statistically different. Low CoQ10 content in the subcutaneous compartment was related to reduced CoQ10 red ( P = 0.02) and CoQ10 ox ( P = 0.05; Fig. 3C ). The redox state ( Fig. 3D ) was similar in these subgroups. Table 3 compares the anthropometric and metabolic characteristics of women with low versus high CoQ10 content in both tissues. As expected, volunteers with a lower   levels of this molecule. The circulating pool of CoQ10 is mostly found in high-and low-density lipoproteins, where it fulfi lls antioxidant roles ( 12 ). The redox state is often used as a marker of oxidative stress and has been shown to be higher in patients with type 2 diabetes ( 21 ). In this study, we examined the regional variations of CoQ10 content and redox state in two adipose tissue depots. We showed for the fi rst time that CoQ10 redox state was fundamentally different among the omental and subcutaneous adipose tissues of lean individuals, despite similar total content. Indeed, we found that the omental depot displayed lower redox state, which is mainly driven by the high content in CoQ10 red . In lean and healthy women, regional variations of these parameters were not linked to adipocyte hypertrophy or infl ammation, suggesting physiological variation of CoQ10 redox status between the intra-abdominal and subcutaneous adipose compartments. We also ruled out the contribution of CoQ10 from food as a major contributor of the adipose CoQ10 pool. Indeed, we established the daily consumption of CoQ10 between 2 and 8 mg/day in this sample of the French Canadian population. These results are similar to a previous study that reported a consumption of 3 to 5 mg of CoQ10 per day in a sample of Danish individuals ( 22 ). However, no association was found between dietary intake and adipose tissue CoQ10 content, suggesting that the intracellular levels may derive mainly from endogenous production. We also observed that overweight volunteers had a reduced CoQ10 tot pool in omental adipose tissue, without modifi cation of the redox state or lipid peroxidation. However, obese women displayed lower concentrations of CoQ10 tot with reduced levels of the antioxidant isoform (CoQ10 red ) and greater LPO content. This indirectly suggests that the depletion in CoQ10 alone is not suffi cient to trigger a sustained oxidative stress response. Nevertheless, CoQ10 red levels and the lower redox state observed in obese women are closely related to LPO production in omental adipose tissue. We can hypothesize that depletion of the CoQ10 tot pool measured in overweight volunteers may predispose omental adipocytes to oxidative damage in response to metabolic stress occurring mostly in obesity. Based on this assumption, a cohort of overweight patients with severe metabolic dysfunctions might also display impaired CoQ10 redox status and oxidative stress in the omental depot.
The loss of omental content in CoQ10 and CoQ10 red was strongly associated with both visceral and subcutaneous fat accumulation. Our results also indirectly suggest that hypertrophic remodeling of the visceral depot plays a critical role in this phenomenon. Moreover, we did not observe any difference in plasma lipids among women with low or high levels of CoQ10 in the omentum, suggesting that modifi cation of CoQ10 tot content is not related to dyslipidemia. However those participants with low CoQ10 content displayed higher IL-6 and CRP plasma levels, suggesting early adipose tissue dysfunction. This group of participants also displayed insulin resistance and hyperinsulinemia without dysglycemia. Taken together, our results suggest that CoQ10 depletion and oxidative stress amount of CoQ10 in the omental depot were more obese and had higher fat mass and fat-free mass. We also found higher visceral and subcutaneous adipose tissue areas, without differences in the visceral-to-subcutaneous area ratio. Even if they were more obese, these volunteers did not display any alteration in plasma lipid levels. However, an increase in mean omental adipocyte diameter, higher IL-6 and CRP plasma levels, and insulin resistance were observed. On the other hand, the group of women with lower CoQ10 content in subcutaneous adipose tissue was not characterized by higher adiposity or changes in body fat distribution. We did not observe any variation of the metabolic parameters except for fasting glucose level, which was slightly higher in women with higher CoQ10 content. We did not fi nd any statistically signifi cant variation of insulin levels or HOMA-IR index in these subgroups.

DISCUSSION
Most of the studies that investigated the link between CoQ10 and cardiometabolic health have focused on plasma related to lipid peroxidation. Moreover, the metabolic profi le of participants with low versus high CoQ10 content in subcutaneous adipose tissue was similar between groups. Despite variation in the absolute CoQ10 red and CoQ10 ox levels, we did not observe modifi cations in plasma lipid levels, insulin resistance, and cytokine secretion. This suggests that the lipophilic antioxidant system in subcutaneous adipose tissue is not a major factor infl uencing metabolic health of women with moderate obesity. Other antioxidant enzymes like catalase, manganese-dependent SOD, or GPx might be involved in the regulation of the intracellular redox status. Indeed, obese Zucker rats had reduced activity of these enzymes in the inguinal fat pad ( 2 ).
The CoQ10 redox state might have different physiological signifi cance depending on the cellular localization on the CoQ10 pool in adipocytes. During mitochondrial respiration, the CoQ10 ox is reduced by complex I or II and carries electrons to complex III. At high mitochondrial membrane potential, a low CoQ10 redox state promotes ROS production. Indeed, higher levels of CoQ10 red in mitochondrial membranes promotes the formation of reactive semiquinone radicals at the Q-binding site of complex I [reviewed in ( 7 )]. The CoQ10 redox state also favors ROS production at the Q o site of the complex III under proper circumstances. On the other hand, ROS derived from complex III are released in the intermembrane space ( 7 ). They can diffuse directly in the cytosol and may act as "signaling ROS" to trigger adaptive responses to oxidative stress. Primary cultures of skin fi broblasts isolated from might be involved in visceral adipose tissue dysfunction leading to insulin resistance and increased risk of developing type 2 diabetes. Surprisingly, we did not fi nd any difference in CoQ10 concentrations in the subcutaneous adipose tissues of overweight versus obese individuals. A previous study found a reduction of CoQ10 levels in subcutaneous samples from obese (BMI from 31 to 40 kg/m 2 ) and morbidly obese (BMI >40 kg/m 2 ) men and women, compared with lean individuals ( 13 ). In that study, overweight patients displayed CoQ10 content that was similar to that of lean volunteers. The conclusion drawn from the latter investigation differs from this work, but could be explained by the nature of the population studied. Most of the women included in the present study had a BMI <40 kg/m 2 . The relation between mean adipocyte size and adiposity level is mostly linear in the subcutaneous depot, until it reaches a plateau in very obese women [reviewed in ( 23 )]. This suggests that most patients included in our investigation still had an important potential for hypertrophic remodeling of the subcutaneous depot despite their excess of body fat mass. If we assume that adipocyte hypertrophy has the same effect on CoQ10 in fat from all anatomical locations, it is possible that adipocyte dysfunction associated with CoQ10 depletion only occurs in females with very high BMI values. We observed a specifi c and signifi cant reduction of the CoQ10 ox content in overweight and obese volunteers, without any variation of CoQ10 red levels or redox state. However, this decrease in CoQ10 ox levels was not patients harboring COQ2 and PDSS2 mutations displayed defects in ATP synthesis and oxidative damage ( 24 ). Otherwise, the CoQ10 red in other cellular membranes displayed antioxidant effects. The cross-sectional and retrospective nature of this study leads to several technical limitations. We were not able to specifi cally measure the CoQ10 content and redox state in separate cell compartments. Moreover the depletion of the CoQ10 pool might affect mitochondrial metabolism and ROS production only under specifi c metabolic conditions. We could not exclude that defects in mitochondrial function could occur in the postprandial state instead of fasting. Moreover the population studied only included a relatively small sample of Caucasian women from 40 to 55 years of age. These results cannot be extrapolated to cohorts of men, pediatric or adolescent obese individuals, and other ethnic groups. Further studies should be conducted to clarify the importance of this phenomenon in the general population.

CONCLUSION
Hypertrophic remodeling of the omental fat depot is related to a smaller CoQ10 pool, which is mostly explained by loss of the antioxidant isoform (CoQ10 red , ubiquinol). This phenomenon is associated with the presence of oxidative stress markers in this depot, systemic low-grade infl ammation, and insulin resistance. However, it was not directly linked to dyslipidemia in this sample of healthy women, suggesting that modifi cations of the CoQ10 redox state and content might be an early mechanism leading to visceral fat dysfunction.