Gene expression in a rarely studied intraabdominal adipose depot, the round ligament, in severely obese women: A pilot study.

Gene expression (qPCR) was compared in round ligament (RL), omental (OME) and mesenteric (MES) ATs from 48 severely obese women (BMI, 54±11 kg/m(2); 38±9 yrs). The mRNA levels of enzymes of lipid metabolism (LPL, HSL, and PDE-3B), cortisol production (11ßHSD-1), adipogenesis (PPAR-γ1/2), thrombosis and inflammation (PAI-1, IL-6, TNF-α and adiponectin) were determined. AT-LPL mRNA was highest in RL. The highest PDE-3B and lowest PAI-1 mRNA levels were observed in RL and MES. The lowest IL-6 and TNF-α and the highest adiponectin and PPAR-g1/2 mRNA levels were found in RL AT. 11ßHSD-1 was highest in RL and OME. A higher lipogenic and adipogenic, and lower pro-inflammatory and pro-thrombotic profiles of the RL suggest a lesser deleterious impact on obesity-related complications.

Gene expression of different adipose tissues of severely obese women with or without a dysmetabolic profile

Despite well-established variations in the health risks posed by visceral vs. subcutaneous abdominal (SCABD) fat depots, surprisingly little is known on the differences within a given adipose tissue (AT) among severely obese patients displaying varying metabolic dysfunction. We thus compared, by quantitative PCR, the expression profile of a number of genes in the SCABD, omental (OME), and mesenteric (MES) depots of severely obese women with (DYS; n = 25) or without (NDYS; n = 23) a dysmetabolic profile. Fasting insulinemia and HOmeostasis Model Assessment-insulin resistance (HOMA-IR) were higher and plasma adiponectin level lower in DYS women (p < 0.05). Among enzymes involved in fatty acid metabolism and local cortisol production, phosphodiesterase-3B expression was lower in SCABD and MES fat, while 11Beta-hydroxysteroid dehydrogenase type 1 mRNA levels were higher in visceral depots of DYS women (p < 0.05). Regarding vascular homeostasis and inflammation, plasminogen activator inhibitor-1 and interleukin-6 mRNA levels were higher in OME fat, while adiponectin expression was lower in SCABD and OME ATs of DYS women (p < 0.05). Finally, HOMA-IR was positively associated with SCABD AT IL6 mRNA, only in DYS women (r = 0.47; p < 0.05). In conclusion, although metabolic and secretory characteristics of all depots vary with subjects’ metabolic profile, we find little evidence for a protective role of SCABD AT and no evidence for a further deleterious role of MES fat in DYS vs. NDYS severely obese women. Regional variation in the overall gene expression revealed that OME and MES fat were more closely related to each other in DYS women, while SCABD and MES depots showed greater resemblance in NDYS women

Gene expression of different adipose tissues of severely obese women with or without a dysmetabolic profile.

Despite well-established variations in the health risks posed by visceral vs. subcutaneous abdominal (SCABD) fat depots, surprisingly little is known on the differences within a given adipose tissue (AT) among severely obese patients displaying varying metabolic dysfunction. We thus compared, by quantitative PCR, the expression profile of a number of genes in the SCABD, omental (OME), and mesenteric (MES) depots of severely obese women with (DYS; n = 25) or without (NDYS; n = 23) a dysmetabolic profile. Fasting insulinemia and HOmeostasis Model Assessment-insulin resistance (HOMA-IR) were higher and plasma adiponectin level lower in DYS women (p < 0.05). Among enzymes involved in fatty acid metabolism and local cortisol production, phosphodiesterase-3B expression was lower in SCABD and MES fat, while 11ß-hydroxysteroid dehydrogenase type 1 mRNA levels were higher in visceral depots of DYS women (p < 0.05). Regarding vascular homeostasis and inflammation, plasminogen activator inhibitor-1 and interleukin-6 mRNA levels were higher in OME fat, while adiponectin expression was lower in SCABD and OME ATs of DYS women (p < 0.05). Finally, HOMA-IR was positively associated with SCABD AT IL6 mRNA, only in DYS women (r = 0.47; p < 0.05). In conclusion, although metabolic and secretory characteristics of all depots vary with subjects' metabolic profile, we find little evidence for a protective role of SCABD AT and no evidence for a further deleterious role of MES fat in DYS vs. NDYS severely obese women. Regional variation in the overall gene expression revealed that OME and MES fat were more closely related to each other in DYS women, while SCABD and MES depots showed greater resemblance in NDYS women.

Effect of adipose tissue volume loss on circulating 25-hydroxyvitamin D levels: results from a 1-year lifestyle intervention in viscerally obese men.

BACKGROUND/OBJECTIVES: Although weight loss has been associated with changes in circulating 25-hydroxyvitamin D (25(OH)D) levels, the quantification of the increase in 25(OH)D levels as a function of adipose tissue volume loss precisely assessed by imaging has not been reported before. The objective of this substudy was to describe the effects of a 1-year lifestyle intervention on plasma 25(OH)D levels. The relationships between changes in 25(OH)D levels and changes in adiposity volume (total and by adipose tissue compartment) were studied. SUBJECTS/METHODS: This intervention study was performed between 2004 and 2006 and participants were recruited from the general community. Sedentary, abdominally obese and dyslipidemic men (n=103) were involved in a 1-year lifestyle modification program. Subjects were individually counseled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500-kcal daily energy deficit and to increase physical activity/exercise habits. Body weight, body composition and fat distribution were assessed by dual-energy X-ray absorptiometry and computed tomography, whereas the 25(OH)D levels were measured with an automated assay. RESULTS: The 1-year intervention resulted in a 26% increase in circulating 25(OH)D (from 48±2 nmol l(-1) or 19±0.8 ng ml(-1) (±s.e.m.) to 58±2 nmol l(-1) or 23±0.8 ng ml(-1), P<0.0001) along with a 26% decrease in visceral adiposity volume (from 1947±458 to 1459±532 cm3). One-year increases in 25(OH)D levels correlated inversely with changes in all adiposity indices, especially Δvisceral (r=-0.36, P<0.0005) and Δtotal abdominal (r=-0.37, P<0.0005) adipose tissue volumes. CONCLUSIONS: These results indicate that there is a linear increase in circulating 25(OH)D levels as a function of adiposity volume loss, and therefore suggest a role of adiposity reduction in the management of obesity-associated vitamin D insufficiency.

Pro-inflammatory phospholipid arachidonic acid/eicosapentaenoic acid ratio of dysmetabolic severely obese women.

BACKGROUND: Fatty acids (FAs) and adipokines such as adiponectin or interleukin-6 (IL-6) are known to modulate inflammation and the development of metabolic syndrome. Whether FA composition assessed in plasma triacylglycerols (TAGs), phospholipids (PLs) and non-esterified fatty acids (NEFAs) and adipose tissue (AT) PLs differed between dysmetabolic and non-dysmetabolic severely obese women remains to be established. Whether the plasma and/or AT arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in the PL sub-fraction may be associated with adipokine AT gene expression needs to be examined. METHODS: FA composition was measured in plasma lipid classes and in the TAG and PL sub-fractions of subcutaneous abdominal and omental ATs of severely obese women paired for age and adiposity but showing a dysmetabolic profile (n = 13) or not (n = 14). FA profile was assessed by gas chromatography. Plasma and AT mRNA concentrations of adiponectin and IL-6 were measured by ELISA and real-time polymerase chain reaction, respectively. RESULTS: Plasma adiponectin and FA concentrations in the NEFA sub-fraction were, respectively, lower and higher in dysmetabolic than in non-dysmetabolic women (p < 0.05). Despite similar FA levels in the PL sub-fraction, the AA/EPA ratio was higher in plasma and ATs (p < 0.005), because of an EPA decrease in plasma and subcutaneous abdominal fat vs. an AA increase in the omental depot. The AA/EPA ratio was negatively associated with adiponectin concentrations in plasma and subcutaneous abdominal AT (0.01 < p < 0.05). CONCLUSIONS: Metabolic dysfunction is associated with a pro-inflammatory phospholipid AA/EPA ratio in plasma and ATs, and an altered adiponectin secretion that could contribute to developing metabolic syndrome.

Obesity, inflammation, and cardiovascular risk.

Obesity, a highly prevalent condition, is heterogeneous with regard to its impact on cardiovascular disease (CVD) risk. Epidemiological observations and metabolic investigations have consistently demonstrated that the accumulation of excess visceral fat is related to an increased risk of CVD as well as several metabolic and inflammatory perturbations. In the past decade, data from several studies have served to emphasize that atherosclerosis has an inflammatory component that may contribute to several key pathophysiological processes. Study data have also highlighted the finding that the expanded visceral fat is infiltrated by macrophages that conduct "cross-talk" with adipose tissue through several significant mechanisms. In this review, we provide, in the context of CVD risk, an up-to-date account of the complex interactions that occur between a dysfunctional adipose tissue phenotype and inflammation.

Physical inactivity, abdominal obesity and risk of coronary heart disease in apparently healthy men and women.

OBJECTIVE: To test the hypothesis that for any given body mass index (BMI) category, active individuals would have a smaller waist circumference than inactive individuals. Our second objective was to examine the respective contribution of waist circumference and physical inactivity on coronary heart disease (CHD) risk. DESIGN: Prospective, population-based study with an 11.4-year follow-up. SUBJECTS: A total of 21 729 men and women aged 45-79 years, residing in Norfolk, UK. METHODS: During follow-up, 2191 CHD events were recorded. Physical activity was evaluated using a validated lifestyle questionnaire that takes into account both leisure-time and work-related physical activity. Waist circumference was measured and BMI was calculated for each participant. RESULTS: For both men and women, we observed that within each BMI category (<25.0, 25-30 and >or=30.0 kg m(-2)), active participants had a lower waist circumference than inactive participants (P<0.001). In contrast, within each waist circumference tertile, BMI did not change across physical activity categories (except for women with an elevated waist circumference). Compared with active men with a low waist circumference, inactive men with an elevated waist circumference had a hazard ratio (HR) for future CHD of 1.74 (95% confidence interval (CI), 1.34-2.27) after adjusting for age, smoking, alcohol intake and parental history of CHD. In the same model and after further adjusting for hormone replacement therapy use, compared with active women with a low waist circumference, inactive women with an elevated waist circumference had an HR for future CHD of 4.00 (95% CI, 2.04-7.86). CONCLUSION: In any BMI category, inactive participants were characterized by an increased waist circumference, a marker of abdominal adiposity, compared with active individuals. Physical inactivity and abdominal obesity were both independently associated with an increased risk of future CHD.

Changes in plasma endocannabinoid levels in viscerally obese men following a 1 year lifestyle modification programme and waist circumference reduction: associations with changes in metabolic risk factors.

AIMS/HYPOTHESIS: We previously reported that the plasma levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), in a cohort of viscerally obese men are directly correlated with visceral adipose tissue (VAT) accumulation and metabolic risk factors including low HDL-cholesterol and high triacylglycerol. It is not known, however, if such correlations persist after vigorous lifestyle interventions that reduce metabolic risk factors. We analysed the changes in endocannabinoid levels in a subsample from the same cohort following a 1 year lifestyle modification programme, and correlated them with changes in VAT and metabolic risk factors. METHODS: Forty-nine viscerally obese men (average age 49 years, BMI 30.9 kg/m(2), waist 107.3 cm) underwent a 1 year lifestyle modification programme including healthy eating and physical activity. Plasma levels of 2-AG and the other most studied endocannabinoid, anandamide, were measured by liquid chromatography-mass spectrometry. Anthropometric and metabolic risk factors, including VAT, insulin resistance and glucose intolerance, HDL-cholesterol and triacylglycerol, were measured. RESULTS: Most risk factors were improved by the intervention, which led to a significant decrease in body weight (-6.4 kg, p < 0.0001), waist circumference (-8.0 cm, p < 0.0001) and VAT (-30%, p < 0.0001), and in plasma 2-AG (-62.3%, p < 0.0001) and anandamide (-7.1%, p = 0.005) levels. The decrease in levels of 2-AG but not those of anandamide correlated with decreases in VAT and triacylglycerol levels, and with the increase in HDL(3)-cholesterol levels. Multivariate analyses suggested that decreases in 2-AG and VAT were both independently associated with decreases in triacylglycerol. CONCLUSIONS/INTERPRETATION: This study shows that a strong correlation exists between 2-AG levels and high plasma triacylglycerol and low HDL(3)-cholesterol in viscerally obese men.

Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men.

OBJECTIVE: The link between excess intra-abdominal adiposity (IAA) and metabolic complications leading to type 2 diabetes and cardiovascular disease is well recognized. Blockade of endocannabinoid action at cannabinoid CB(1) receptors was shown to reduce these complications. Here, we investigated the relationship between IAA, circulating endocannabinoid levels and markers of cardiometabolic risk in male obese subjects. DESIGN, SUBJECTS AND MEASUREMENTS: Fasting plasma levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), were measured by liquid chromatography-mass spectrometry in a study sample of 62 untreated asymptomatic men with body mass index (BMI) from 18.7 to 35.2 kg/m(2). RESULTS: Plasma 2-AG, but not AEA, levels correlated positively with BMI, waist girth, IAA measured by computed tomography, and fasting plasma triglyceride and insulin levels, and negatively with high-density lipoprotein cholesterol and adiponectin levels. Obese men with similar BMI values (> or =30 kg/m(2)) but who markedly differed in their amount of IAA (< vs > or = 130 cm(2), n=17) exhibited higher 2-AG levels in the presence of high IAA. No difference in 2-AG concentrations was observed between obese men with low levels of IAA vs nonobese controls. CONCLUSIONS: These results provide evidence for a relationship in men between a key endocannabinoid, 2-AG, and cardiometabolic risk factors, including IAA.

Contribution of CB1 blockade to the management of high-risk abdominal obesity.

The worldwide increase in the prevalence of type 2 diabetes represents a tremendous challenge for our healthcare system, especially if we consider that this phenomenon is largely explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting that abdominal adipose tissue is the fat depot that conveys the greatest risk of metabolic complications. This cluster of metabolic abnormalities has been referred to as the metabolic syndrome and this condition is largely the consequence of abdominal obesity, especially when accompanied by a high accumulation of visceral adipose tissue. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of coronary heart disease beyond the presence of traditional risk factors. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of coronary heart disease and of type 2 diabetes. The recent discovery of the endocannabinoid-CB1 receptor system and of its impact on the regulation of energy metabolism represents a significant advance, which will help physicians target abdominal obesity and its related metabolic complications. In this regard, studies have shown that rimonabant therapy (the first developed CB1 blocker) could be useful for the management of clustering cardiovascular disease risk factors in high-risk abdominally obese patients through its effects not only on energy balance but also on adipose tissue metabolism. For instance, the presence of CB1 receptors in adipose tissue and the recently reported effect of rimonabant on adiponectin production by adipose cells may represent a key factor responsible for the weight loss-independent effect of this CB1 blocker on cardiometabolic risk variables.

Effect of type 2 diabetes on various electrophoretic characteristics of low-density lipoprotein particles in women.

AIMS/HYPOTHESIS: Coronary heart disease represents the leading cause of death in type 2 diabetic patients. As the small, dense LDL phenotype is a typical feature of the dyslipidaemic state found in type 2 diabetes, this characteristic could be an important mediator of the elevated coronary heart disease risk in this condition. We have therefore studied the effect of type 2 diabetes on various electrophoretic characteristics of LDL particles. METHODS: Potential differences in LDL peak particle size and in concentration of LDL cholesterol in small (<255 A) and large (>260 A) LDL particles were assessed by polyacrylamide gradient gel electrophoresis among 183 non-diabetic and 56 type 2 diabetic women. RESULTS: LDL peak particle size was significantly smaller in type 2 diabetic women than in non-diabetic women (p<0.0001). In addition, the proportion of small LDL particles (<255 A) was higher in type 2 diabetic women, whereas the proportion of large LDL particles (>260 A) was lower than in non-diabetic women (p<0.0002). Type 2 diabetic women also had the highest waist circumference and triglyceride levels (p<0.03). When subgroups of non-diabetic and type 2 diabetic women were individually matched (n=41) for similar waist circumference and triglyceride levels, the differences initially found in LDL peak particle size and in the proportion of small and large LDL particles remained significantly different between the two groups (p<0.01). CONCLUSIONS/INTERPRETATION: These results provide evidence that type 2 diabetes may have an independent effect on LDL peak particle size and on the proportion of small and large LDL particles.

Effects of micronized fenofibrate versus atorvastatin in the treatment of dyslipidaemic patients with low plasma HDL-cholesterol levels: a 12-week randomized trial.

BACKGROUND: Studies have suggested that raising low levels of high-density lipoprotein cholesterol (HDL-C) may be an important target for the prevention of coronary heart disease. OBJECTIVE: To compare the ability of micronized fenofibrate and atorvastatin to increase plasma HDL-C levels. DESIGN: Multicentre, randomized open-label study. Settings. The study was conducted in 19 centres across the UK and Canada. SUBJECT: One hundred and eighty-one patients were randomized and the full analysis set included 165 nondiabetic patients with low HDL-C (women <46 mg dL-1, i.e. 1.2 mmol L-1 and men <43 mg dL-1, i.e. 1.1 mmol L-1): 86 patients in the atorvastatin group and 79 patients in the micronized fenofibrate group. Interventions. Micronized fenofibrate (200 mg day-1, 87 patients) or atorvastatin (10 mg day-1, 94 patients) for a period of 12 weeks. Main outcome measures. Percent change in HDL-C levels. RESULT: After 12 weeks of treatment, the mean percent change from baseline in HDL-C was significantly higher in the micronized fenofibrate group (13.3%) compared with the atorvastatin group (5.3%, P=0.0003). The magnitude of such relative change was inversely related to the baseline HDL-C levels only in the micronized fenofibrate group. Furthermore, in the fenofibrate treatment group, 50.9% of the patients (29 of 57 patients) with a baseline HDL-C <40 mg dL-1 achieved a plasma HDL-C level above 40 mg dL-1 after 12 weeks of treatment versus 27.9% of the patients (19 of 68 patients) in the atorvastatin group (P=0.01). CONCLUSIONS: On the basis of (1) the greater impact of fenofibrate than atorvastatin on HDL-C levels and (2) the greater proportion of dyslipidemic patients achieving HDL-C levels above 40 mg dL-1 with fenofibrate than atorvastatin, it is suggested that micronized fenofibrate should be considered as a good therapeutic option to treat dyslipidemic patients with low HDL-C and moderately elevated LDL-C concentrations.

Is the gender difference in LDL size explained by the metabolic complications of visceral obesity?

BACKGROUND: Several studies have reported a significant gender difference in low-density lipoprotein (LDL) size, with men being characterized by smaller, denser LDL particles than women, and it has been suggested that the contribution of the greater accumulation of visceral adipose tissue in men compared with women may be a factor potentially contributing to the gender difference in LDL heterogeneity. MATERIALS AND METHODS: We measured LDL particle size by 2-16% nondenaturing polyacrylamide gradient gel electrophoresis in 299 men and 231 women in whom visceral adipose tissue accumulation was measured by computed tomography. A fasting plasma lipoprotein-lipid profile was also obtained in all subjects. RESULTS: Overall, the men were characterized by a more deteriorated metabolic risk factor profile, which included higher plasma insulin and triglyceride levels, a greater visceral adipose tissue accumulation (P < 0.001) and smaller LDL particles (251.7 +/- 5.2 vs. 254.4 +/- 4.2 A, P < 0.0001). This gender difference in LDL peak particle diameter remained significant (252.4 +/- 4.3 vs. 253.5 +/- 4.3 A, P < 0.01) after adjustment for sex-specific differences in plasma triglyceride levels by covariance analysis. Significant negative correlations were noted between the LDL particle diameter and the triglyceride concentrations in both genders (r = -0.52 and r = -0.36, P < 0.0001 for the men and women, respectively), with no gender difference in this relationship being found. However, viscerally obese women (visceral adipose tissue levels > 100 cm2) with increased plasma triglyceride concentrations (> 2.0 mmol L-1) still had larger LDL particles than viscerally obese men with a similar elevation in their triglyceride levels (251.6 +/- 4.9 vs. 248.7 +/- 4.5 A, P < 0.01). CONCLUSIONS: Results of the present study suggest that the reduced LDL particle size observed in men compared with women cannot be entirely explained by their higher visceral adipose tissue accumulation and increased plasma triglyceride levels. Moreover, the gender difference in LDL size could be influenced, at least in part, by the severity of the hypertriglyceridaemic state.

Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.

BACKGROUND: Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)-low HDL-C dyslipidemia. METHODS: A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. RESULTS: The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles (P<.001). Greater differences in features of the insulin resistance syndrome (insulinemia, apolipoprotein B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles of the LDL-C/HDL-C ratio. CONCLUSION: Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio.

Effect of a low-glycaemic index--low-fat--high protein diet on the atherogenic metabolic risk profile of abdominally obese men.

It has been suggested that the current dietary recommendations (low-fat-high-carbohydrate diet) may promote the intake of sugar and highly refined starches which could have adverse effects on the metabolic risk profile. We have investigated the short-term (6-d) nutritional and metabolic effects of an ad libitum low-glycaemic index-low-fat-high-protein diet (prepared according to the Montignac method) compared with the American Heart Association (AHA) phase I diet consumed ad libitum as well as with a pair-fed session consisting of the same daily energy intake as the former but with the same macronutrient composition as the AHA phase I diet. Twelve overweight men (BMI 33.0 (sd 3.5) kg/m2) without other diseases were involved in three experimental conditions with a minimal washout period of 2 weeks separating each intervention. By protocol design, the first two conditions were administered randomly whereas the pair-fed session had to be administered last. During the ad libitum version of the AHA diet, subjects consumed 11695.0 (sd 1163.0) kJ/d and this diet induced a 28 % increase in plasma triacylglycerol levels (1.77 (sd 0.79) v. 2.27 (sd 0.92) mmol/l, P<0.05) and a 10 % reduction in plasma HDL-cholesterol concentrations (0.92 (sd 0.16) v. 0.83 (sd 0.09) mmol/l, P<0.01) which contributed to a significant increase in cholesterol:HDL-cholesterol ratio (P<0.05), this lipid index being commonly used to assess the risk of coronary heart disease. In contrast, the low-glycaemic index-low-fat-high-protein diet consumed ad libitum resulted in a spontaneous 25 % decrease (P<0.001) in total energy intake which averaged 8815.0 (sd 738.0) kJ/d. As opposed to the AHA diet, the low-glycaemic index-low-fat-high-protein diet produced a substantial decrease (-35 %) in plasma triacylglycerol levels (2.00 (sd 0.83) v. 1.31 (sd 0.38) mmol/l, P<0.0005), a significant increase (+1.6 %) in LDL peak particle diameter (251 (sd 5) v. 255 (sd 5) A, P<0.02) and marked decreases in plasma insulin levels measured either in the fasting state, over daytime and following a 75 g oral glucose load. During the pair-fed session, in which subjects were exposed to a diet with the same macronutrient composition as the AHA diet but restricted to the same energy intake as during the low-glycaemic index-low-fat-high-protein diet, there was a trend for a decrease in plasma HDL-cholesterol levels which contributed to the significant increase in cholesterol:HDL-cholesterol ratio noted with this condition. Furthermore, a marked increase in hunger (P<0.0002) and a significant decrease in satiety (P<0.007) were also noted with this energy-restricted diet. Finally, favourable changes in the metabolic risk profile noted with the ad libitum consumption of the low-glycaemic index-low-fat-high-protein diet (decreases in triacyglycerols, lack of increase in cholesterol:HDL-cholesterol ratio, increase in LDL particle size) were significantly different from the response of these variables to the AHA phase I diet. Thus, a low-glycaemic index-low-fat-high-protein content diet may have unique beneficial effects compared with the conventional AHA diet for the treatment of the atherogenic metabolic risk profile of abdominally obese patients. However, the present study was a short-term intervention and additional trials are clearly needed to document the long-term efficacy of this dietary approach with regard to compliance and effects on the metabolic risk profile.

Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity.

Reduced plasma HDL cholesterol concentration has been associated with an increased risk of coronary heart disease. However, a low HDL cholesterol concentration is usually not observed as an isolated disorder because this condition is often accompanied by additional metabolic alterations. The objective of this study was to document the relevance of assessing HDL particle size as another feature of the atherogenic dyslipidemia found among subjects with visceral obesity and insulin resistance. For that purpose, an average HDL particle size was computed by calculating an integrated HDL particle size using nondenaturing 4-30% gradient gel electrophoresis. Potential associations between this average HDL particle size versus morphometric and metabolic features of visceral obesity were examined in a sample of 238 men. Results of this study indicated that HDL particle size was a significant correlate of several features of an atherogenic dyslipidemic profile such as increased plasma TG, decreased HDL cholesterol, high apolipoprotein B, elevated cholesterol/HDL cholesterol ratio, and small LDL particles as well as increased levels of visceral adipose tissue (AT) (0.33 < or = absolute value of r < or = 0.61, P < 0.0001). Thus, men with large HDL particles had a more favorable plasma lipoprotein-lipid profile compared with those with smaller HDL particles. Furthermore, men with large HDL particles were also characterized by reduced overall adiposity and lower levels of visceral AT as well as reduced insulinemic-glycemic responses to an oral glucose load. In conclusion, small HDL particle size appears to represent another feature of the high TG- low HDL cholesterol dyslipidemia found in viscerally obese subjects characterized by hyperinsulinemia.

Is the relationship between adipose tissue and waist girth altered by weight loss in obese men?

OBJECTIVE: The aim of the present study was to examine whether the association of waist girth to visceral adipose tissue (AT) accumulation was altered by weight loss in abdominally obese men. RESEARCH METHODS AND PROCEDURES: We studied 45 dyslipidemic abdominally obese men (45.4 +/- 6.2 years of age; body mass index [BMI], 31.3 +/- 3.0 kg/m(2); waist circumference, 103.4 +/- 7.6 cm; total cholesterol, <6.72 mM; triglycerides, > or =1.7 mM but < or =5.65 mM; high density lipoprotein cholesterol, < or =1.2 mM). Each of them followed nutritional recommendations combined with a prescription of gemfibrozil (1200 mg/d) or a placebo for 1 year. After 6 months, a training exercise program was added at a frequency of four sessions of 60 minutes per week at 50% of maximal oxygen uptake. RESULTS: In response to the 1-year intervention program, men showed significant reductions in body weight, BMI, waist circumference, and in the partial volume of visceral and abdominal subcutaneous AT measured from two abdominal computed tomography scans performed at lumbar vertebra (L)2 to L3 and L4 to L5 levels. No change in waist-to-hip ratio was observed. Changes in visceral AT were strongly correlated with changes in body weight, BMI, and waist circumference (0.83 < r < 0.85; p < 0.001). However, a weak association was noted between waist-to-hip ratio and changes in visceral AT (r = 0.40; p < 0.05). There was no change in slopes or in intercepts before and after treatment in the relationships between volume or area of abdominal AT and anthropometric markers. DISCUSSION: Despite a greater level of the partial volume of subcutaneous AT than of the partial volume of visceral AT at baseline (p < 0.001), the greater relative reduction in the visceral AT volume in comparison with the subcutaneous AT volume suggested a preferential mobilization of visceral AT with weight loss in these abdominally obese men. The close relationship between changes in the partial volume of visceral AT and changes in cross-sectional areas of visceral AT measured at L2 to L3 (r = 0.94; p < 0.001) or L4 to L5 (r = 0.88; p < 0.001) suggests that a single computed tomography scan performed at L2 to L3 or L4 to L5 could predict changes in the partial volume of visceral AT secondary to weight loss.

[Fat distribution and metabolism]. / Distribution et métabolisme des masses grasses.

It is well known that adipose tissue distribution is an important factor involved in the etiology of type 2 diabetes and cardiovascular diseases. Adipose tissue distribution is obviously different between men and women, men being prone to accumulate their excess of energy in the abdominal region, more specifically in the intra-abdominal depot (visceral) whereas women show a selective deposition of adipose tissue in the gluteo-femoral region. Several studies have demonstrated an association between age and adipose tissue distribution and a selective deposition of visceral adipose tissue has been reported with age, in both men and women. In this regard, the menopause transition also appears to be a factor associated with an accelerated accumulation of abdominal adipose tissue. This increase in visceral adipose tissue has been suggested to play a significant role in the etiology of metabolic complications increasing the risk of type 2 diabetes and cardiovascular diseases. However, a selective mobilization of visceral adipose tissue in response to a weight loss program has been noted among viscerally obese patients, this reduction in visceral adipose tissue being associated with improvements in the lipoprotein-lipid profile and insulin sensitivity. Thus, the distribution of adipose tissue is an important factor to take into account in the evaluation of the patient. Furthermore, the amount of abdominal adipose tissue should also be considered as an important therapeutic target for the optimal management of cardiovascular disease risk.

Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity.

Recent studies have suggested that elevated plasma C-reactive protein (CRP) levels are associated with the features of insulin resistance syndrome. In the present study, we have examined the contribution of body composition measured by hydrostatic weighing and of abdominal adipose tissue (AT) accumulation assessed by computed tomography to the variation in plasma CRP levels associated with atherogenic dyslipidemia of the insulin resistance syndrome in a sample of 159 men, aged 22 to 63 years, covering a wide range of adiposity (body mass index values from 21 to 41 kg/m(2)). Plasma CRP levels showed positive and significant correlations with body fat mass (r=0.41, P<0.0001), waist girth (r=0.37, P<0.0001), and visceral AT accumulation measured by computed tomography at L4 to L5 (r=0.28, P<0.0003). Although CRP levels were associated with plasma insulin levels measured in the fasting state and after a 75-g oral glucose load, no significant correlations were found with plasma lipoprotein levels. Finally, comparison of body fatness, of abdominal fat accumulation, and of the features of the insulin resistance syndrome across quintiles of CRP revealed major differences in body fatness and in indices of abdominal AT accumulation between the lowest and the highest CRP quintiles, whereas no significant differences were found for variables of the plasma lipoprotein-lipid profile. These results suggest that obesity and abdominal AT accumulation are the critical correlates of elevated plasma CRP levels found in men with atherogenic dyslipidemia of the insulin resistance syndrome.

Deterioration of the metabolic risk profile in women. Respective contributions of impaired glucose tolerance and visceral fat accumulation.

OBJECTIVE: To determine whether the impaired glucose tolerance (IGT) state contributes to the deterioration of the metabolic profile in women after taking into account the contribution of visceral adipose tissue (AT) accumulation, as measured by computed tomography. RESEARCH DESIGN AND METHODS: We studied 203 women with normal glucose tolerance (NGT) and 46 women with IGT, defined as a glycemia between 7.8 and 11.1 mmol/l measured 2 h after a 75-g oral glucose load. RESULTS: Women with IGT were characterized by a higher visceral AT accumulation and by higher concentrations of fasting plasma glucose, insulin, and C-peptide as well as by higher plasma concentrations of cholesterol, triglycerides, and apolipoprotein B (apoB) and by greater cholesterol-to-HDL-cholesterol ratio, reduced LDL peak particle size, lower HDL-cholesterol and HDL2-cholesterol concentrations, and higher blood pressure (P < 0.01) than women with NGT. When we matched 27 pairs of women for visceral AT and fat mass as well as for menopausal status, differences previously found in LDL-cholesterol, LDL peak particle size, HDL-cholesterol, and HDL2-cholesterol concentrations as well as in the cholesterol-to-HDL-cholesterol ratio and blood pressure were eliminated, whereas triglyceride concentrations remained significantly higher in women with IGT. CONCLUSIONS: A high visceral AT accumulation is a major factor involved in the deterioration of many metabolic variables in women with IGT, with the notable exception of triglyceride concentrations, which remained significantly different between women with NGT and women with IGT after adjustment for visceral fat.