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Biomedical subjects

S Lemieux

Publications and source records attributed to S Lemieux.

At least 19 recordsLinked to original sources

Disinhibition, as assessed by the Three-Factor Eating Questionnaire, is inversely related to psychological well-being in postmenopausal women.

UNLABELLED: Psychological correlates of obesity remain under controversy. As eating behaviors and dieting history have been previously related to obesity status, these dietary variables may contribute to identify overweight and obese individuals who are at higher risk of having an impaired psychological well-being. OBJECTIVE: The main purpose of this cross-sectional study was to verify the hypothesis of a relationship between weight status and psychological well-being, and to examine whether cognitive dietary restraint, disinhibition, susceptibility to hunger and dieting history could be related to psychological well-being. DESIGN AND SUBJECTS: In a sample of 101 postmenopausal women, we performed anthropometric measurements (weight, height and body mass index (BMI)), and measured psychological well-being (PER Questionnaire). The Three-Factor Eating Questionnaire (TFEQ) and a questionnaire about dieting history (dieters: had already been on a diet; non-dieters: had never been on a diet) were also administrated. RESULTS: A trend for a significant relationship was observed between BMI and psychological well-being (r=-0.17; P=0.08). Significant negative relationships were observed for disinhibition, susceptibility to hunger and all their subscales with psychological well-being (-0.28</=r</=-0.48), whereas no significant differences in psychological well-being were observed between dieters and non-dieters. Finally, women displaying a higher score for habitual susceptibility to disinhibition (which is the subscale of TFEQ that was the most closely related to psychological well-being) had a lower level of psychological well-being, regardless of their weight status. CONCLUSION: These results show that, as well as being related to weight status, TFEQ-factors are also related to psychological well-being. More specifically, individuals who display higher levels of disinhibition may be at higher risk of having an impaired psychological well-being.

Aged↗

Muscle adiposity and body fat distribution in type 1 and type 2 diabetes: varying relationships according to diabetes type.

OBJECTIVE: To compare the relationships between markers of total and regional adiposity with muscle fat infiltration in type 1 diabetic and type 2 diabetic subjects and their respective nondiabetic controls, and to document these relationships in type 1 diabetic subjects. DESIGN: Cross-sectional study. SUBJECTS: In total, 86 healthy, with type 1 diabetes, type 2 diabetes or control subjects. Each diabetic group was matched for age, sex and body mass index with its respective nondiabetic control group. MEASUREMENTS: Measures of body composition (hydrodensitometry), fat distribution (waist circumference, abdominal and mid-thigh computed tomography scans) and blood lipid profiles were assessed. RESULTS: Low attenuation mid-thigh muscle surface correlated similarly with markers of adiposity and body composition in all groups, regardless of diabetes status, except for visceral adipose tissue and waist circumference. Indeed, relationships between visceral adiposity and muscle adiposity were significantly stronger in type 2 vs type 1 diabetic subjects (P<0.05 for comparison of slopes). In addition, in well-controlled type 1 diabetic subjects (mean HbA(1c) of 6.8%), daily insulin requirements tended to correlate with low attenuation mid-thigh muscle surface, a specific component of fat-rich muscle (r=0.36, P=0.08), but not with glycemic control (HbA(1c)). CONCLUSION: This study suggests that the relationship of central adiposity and muscle adiposity is modulated by diabetes status and is stronger in the insulin resistant diabetes type (type 2 diabetes). In well-controlled nonobese type 1 diabetic subjects, the relationship between muscle fat accumulation and insulin sensitivity was also maintained.

Adiposity↗

fMRI Measures of perceptual filling-in in the human visual cortex.

Filling-in refers to the tendency of stabilized retinal stimuli to fade and become replaced by their background. This phenomenon is a good example of central brain mechanisms that can selectively add or delete information to/from the retinal input. Importantly, such cortical mechanisms may overlap with those that are used more generally in visual perception. In order to identify cortical areas that contribute to perceptual filling-in, we used functional magnetic resonance imaging to image activity in the visual cortex while subjects experienced filling-in. Nine subjects viewed an achromatic disc with slightly higher luminance than the background and indicated the presence or absence of filling-in by a keypress. The disc was placed in either the upper or lower left quadrant. Similar high-contrast stimuli were used to map out the retinotopic representation of the disc. Unexpectedly, the lower-field high-contrast stimulus produced more parietal cortex activation than the upper-field condition, indicating preferential representation of the lower field by attentional control mechanisms. During perceptual filling-in, we observed significant contralateral reductions in activation in lower-tier retinotopic areas V1 and V2. In contrast, increased activation was consistently observed in visual areas V3A and V4v, higher-level cortex in the intraparietal sulcus, posterior superior temporal sulcus, and the ventral occipital-temporal region, as well as the pulvinar. The filling-in activation pattern was remarkably similar for both the upper- and lower-field conditions. Behaviorally, filling-in was reported to be easier for the lower visual field, and filling-in periods were longer for the lower than the upper quadrant. We suggest this behavioral asymmetry may be partially due to the preferential parietal representation of the lower field. The results lead us to propose that perceptual filling-in recruits high-level control mechanisms to reconcile competing percepts, and alters the normal image-related signals at the first stages of cortical processing. Moreover, the overall pattern of activation during filling-in resembles that seen in other studies of perceptually bistable stimuli, including binocular rivalry, indicating common control mechanisms.

Adult↗

High normal 2-hour plasma glucose is associated with insulin sensitivity and secretion that may predispose to type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to evaluate differences in insulin sensitivity, insulin secretion and risk factors for cardiovascular disease between subjects with a 2-h plasma glucose (2hPG) level within the normal range (NPG) and subjects with IGT, following a 75-g OGTT. We also aimed to determine the respective contributions made by 2hPG and fasting plasma glucose to the metabolic risk profile. METHODS: We compared cardiovascular risk factors and insulin sensitivity and insulin secretion by using several indices calculated using measurements obtained during an OGTT. Subjects (n=643, age 18-71 years) were participants in the Quebec Family Study and were categorised according to 2hPG as having low NPG (2hPG <5.6 mmol/l, the group median for normal values), high NPG (2hPG 5.6-7.7 mmol/l) or IGT (2hPG 7.8-11.0 mmol/l). Subjects with type 2 diabetes were excluded from all analyses. RESULTS: Beta cell function and insulin sensitivity progressively decreased with increasing 2hPG. Compared with subjects with low NPG, subjects with high NPG were more insulin-resistant (p<0.05) and had reduced insulin secretion (adjusted for insulin resistance) (p<0.001). They also had higher plasma triglyceride concentrations (p<0.01) and cholesterol:HDL cholesterol ratios (p<0.05). These differences remained even after adjustment for age, sex, BMI and waist circumference. Multivariate analyses showed that 2hPG was closely associated with risk factors for diabetes and with cardiovascular variables, including triglycerides (p<0.0001) and apolipoprotein B (p<0.01). CONCLUSIONS/INTERPRETATION: These results show that deteriorations in glucose-insulin metabolism, which may predispose individuals to type 2 diabetes and cardiovascular disease, are already present in subjects with 2hPG concentrations within the high normal range. Independently of obesity, 2hPG was found to explain, in part, the variance observed in cardiovascular and diabetes risk factors. In addition, elevated 2hPG was associated with metabolic alterations that appear to be the most detrimental to metabolic health. Thus, 2hPG values within the high normal range may be an important marker for the identification of people at risk of complications related to type 2 diabetes.

Adolescent↗

Plasma concentrations of apolipoprotein B are modulated by a gene--diet interaction effect between the LFABP T94A polymorphism and dietary fat intake in French-Canadian men.

Hyperapobetalipoproteinemia is a common feature of the metabolic syndrome and could result from the interaction between genetic and dietary factors. The objective of this study was to verify whether dietary fat intake interacts with the T94A polymorphism of the liver fatty acid-binding protein (LFABP) gene to modulate plasma apolipoprotein (apo) B levels. Dietary fat and saturated fat intakes were obtained by a dietitian-administered food frequency questionnaire and the LFABP T94A genotype was determined by a PCR-RFLP based method in 623 French-Canadian men recruited through the Chicoutimi Lipid Clinic (279 T94/T94, 285 T94/A94, and 59 A94/A94). The LFABP T94A polymorphism was not associated with plasma apo B levels when fat intake was not taken into consideration. However, in a model including the polymorphism, fat intake expressed as a percentage of total energy intake, the interaction term and covariates, the variance in apo B concentrations was partly explained by the LFABP T94A polymorphism (5.24%, p = 0.01) and by the LFABP T94A*fat interaction (6.25%, p = 0.005). Results were similar when saturated fat replaced fat intake in the model (4.49%, p = 0.02 for LFABP T94A and 6.43%, p = 0.004 for the interaction). Moreover, in men consuming more than 30% of energy from fat, the odds ratio for having plasma apo B levels above 1.04 g/L for A94 carriers was of 0.40 (p = 0.02) compared to T94/T94 homozygotes. Results were similar for carriers of the A94 allele consuming more than 10% of energy from saturated fat (OR: 0.32, p = 0.005). In conclusion, T94/T94 exhibit higher apo B levels whereas carriers of the A94 allele seem to be protected against high apo B levels when consuming a high fat and saturated fat diet. These findings reinforce the importance to take into account gene-diet interactions in the prevention and management of the metabolic syndrome.

Adult↗

Impaired fasting glucose vs. glucose intolerance in pre-menopausal women: distinct metabolic entities and cardiovascular disease risk?

BACKGROUND: Impaired glucose tolerance (IGT) is associated with an increased cardiovascular disease risk. Less is known about cardiovascular disease risk among subjects with impaired fasting glucose (IFG) or with combined IFG and IGT. AIMS: To compare body composition, body fat distribution, plasma glucose-insulin homeostasis and plasma lipid-lipoprotein profile between pre-menopausal women having either a normal glucose tolerance (NGT), isolated IFG, isolated IGT or combined IFG and IGT. METHODS: Three hundred and thirty-four women with NGT, 11 women with IFG, 35 women with IGT and 10 women with both IFG and IGT were studied. RESULTS: Women with IFG were characterized by a higher visceral adipose tissue (AT) accumulation than women with NGT (P < 0.05). Also, they were characterized by a higher subcutaneous AT area and by higher body fat mass than NGT and IGT women (P < 0.05). However, their lipid-lipoprotein profile was comparable with that of NGT women, except for reduced HDL-cholesterol concentrations (P < 0.05). After adjustment for visceral AT, women with IFG had lower total cholesterol, LDL-cholesterol and apolipoprotein B (apoB) levels than the three other groups. They also had lower HDL(2)-cholesterol than NGT women and lower total cholesterol/HDL-cholesterol ratio than IGT women. Women with IGT showed higher triglyceride and apoB concentrations and a higher total cholesterol/HDL-cholesterol ratio than women with NGT (P < 0.05). Overall, women with combined IFG and IGT showed body fatness characteristics and alterations in their metabolic risk profile which were essentially similar to women with isolated IGT. CONCLUSIONS: These results indicate that there are significant differences in anthropometric and metabolic variables between pre-menopausal women with IFG vs. IGT and that the association between body fatness-body fat distribution indices and the metabolic profile may differ between IFG and IGT women.

Adolescent↗

Do 6-y changes in eating behaviors predict changes in body weight? Results from the Québec Family Study.

OBJECTIVE: This study was performed to examine changes in eating behaviors as assessed by the three-factor eating questionnaire (TFEQ) and to quantify the potential associations between these eating behaviors and body weight changes in a 6-follow-up study. DESIGN AND SUBJECTS: Prospective study performed in men and women who were tested twice (Visit 1=1989-1995 and Visit 2=6 y later) in the Québec Family Study (QFS). RESULTS: Women were more restrained and less hungry than men. To reduce food intake, women relied more on strategic dieting behavior and avoided more fattening food. However, they had higher emotional and situational susceptibility to eat than men. Significant decreases in the disinhibition score were noted over time in women (P<0.01), which resulted from a decrease in habitual susceptibility behavior to increase food intake. In men, we observed an increase in the avoidance of fattening food (P<0.05). In both genders, we found that the 6-y change in restraint behavior was negatively correlated with body weight changes (P<0.05). In women, a high restraint behavior seems to promote weight gain, whereas in men, it is associated with the opposite trend. CONCLUSION: These results suggest that variables reflecting some eating behaviors are associated with body weight changes in a free-living context. However, these behaviors are expressed differently between men and women. These behaviors should be considered in clinical interventions for individuals seeking a better body weight control.

Adult↗

Cutting edge: Ly49A inhibits TCR/CD3-induced apoptosis and IL-2 secretion.

To evaluate the importance of Ly49A on TCR-induced cellular events, we established clones of the 1F2 T cell hybridoma expressing either Ly49A or a chimeric version, Ly49A/H, where the Ly49A cytoplasmic domain has been replaced by the Ly49H cytoplasmic domain. Ligation of Ly49A, but not Ly49A/H, with its ligand H-2D(d) or anti-Ly49A mAbs caused a specific inhibition of TCR/CD3-induced IL-2 secretion. Moreover, flow cytometry analysis of hypodiploid DNA and annexin V binding revealed that ligation of Ly49A protected cells from apoptosis induced by anti-CD3 mAbs or Ag. In contrast, ligation of the Ly49A/H chimeric receptor had no antiapoptotic effect. In addition, engagement of Ly49A selectively inhibited TCR-induced Fas ligand expression whereas TCR-induced Fas expression was not significantly affected. Expression of Ly49 inhibitory receptors on T cells may represent an important mechanism for the regulation of T cell survival in vivo by inhibiting TCR-induced apoptosis and IL-2 secretion.

Animals↗

Quantitative analysis of nucleic acid three-dimensional structures.

A new computer program to annotate DNA and RNA three-dimensional structures, MC-Annotate, is introduced. The goals of annotation are to efficiently extract and manipulate structural information, to simplify further structural analyses and searches, and to objectively represent structural knowledge. The input of MC-Annotate is a PDB formatted DNA or RNA three-dimensional structure. The output of MC-Annotate is composed of a structural graph that contains the annotations, and a series of HTML documents, one for each nucleotide conformation and base-base interaction present in the input structure. The atomic coordinates of all nucleotides and the homogeneous transformation matrices of all base-base interactions are stored in the structural graph. Symbolic classifications of nucleotide conformations, using sugar puckering modes and nitrogen base orientations around the glycosyl bond, and base-base interactions, using stacking and hydrogen bonding information, are introduced. Peculiarity factors of nucleotide conformations and base-base interactions are defined to indicate their marginalities with all other examples. The peculiarity factors allow us to identify irregular regions and possible stereochemical errors in 3-D structures without interactive visualization. The annotations attached to each nucleotide conformation include its class, its torsion angles, a distribution of the root-mean-square deviations with examples of the same class, the list of examples of the same class, and its peculiarity value. The annotations attached to each base-base interaction include its class, a distribution of distances with examples of the same class, the list of examples of the same class, and its peculiarity value. The distance between two homogeneous transformation matrices is evaluated using a new metric that distinguishes between the rotation and the translation of a transformation matrix in the context of nitrogen bases. MC-Annotate was used to build databases of nucleotide conformations and base-base interactions. It was applied to the ribosomal RNA fragment that binds to protein L11, which annotations revealed peculiar nucleotide conformations and base-base interactions in the regions where the RNA contacts the protein. The question of whether the current database of RNA three-dimensional structures is complete is addressed.

Base Pairing↗

Inhibition of tumour growth and metastasis of human fibrosarcoma cells HT-1080 by monoclonal antibody BCD-F9.

BCD-F9 is a murine IgG(2a) monoclonal antibody (mAb) that recognises a conformational epitope found on the surface of many human tumour cells. The aim of this study was to investigate the ability of BCD-F9 to recognise a variety of neoplastic cell lines and to test BCD-F9 in vivo for anticancer activity in subcutaneous (s.c.) and metastatic tumour models. Intravenous (i.v.) administration of BCD-F9 in CD-1 nude mice xenografted s.c. with human HT-1080 cells led to a significant inhibition of tumour growth. We demonstrated that BCD-F9 administrated i.v. significantly prolonged the life-span of CD-1 nude mice inoculated i.v. with the same tumour cell line that induces aggressive lung metastases in the untreated mice. We also investigated the antitumour activity of BCD-F9 in vitro in antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ADCMC) assays. The effector cell subpopulations were obtained by macrophage stimulation (thioglycollate) or natural killer (NK) cell enrichment (negative selection). BCD-F9 was found to be effective in mediating tumour cell killing in vitro by ADCC and ADCMC mechanisms. These results suggest that the mAb BCD-F9 can have a potential use in immunotherapy for treatment of tumours of different origin.

Animals↗

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.

Adipose Tissue↗

n-3 Fatty acids and cardiovascular disease risk factors among the Inuit of Nunavik.

BACKGROUND: Inuit traditionally consume large amounts of marine foods rich in n-3 fatty acids. Evidence exists that n-3 fatty acids have beneficial effects on key risk factors for cardiovascular disease. OBJECTIVE: Our goal was to verify the relation between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among the Inuit of Nunavik, Canada. DESIGN: The study population consisted of 426 Inuit aged 18-74 y who participated in a 1992 health survey. Data were obtained through home interviews and clinical visits. Plasma samples were analyzed for phospholipid fatty acid composition. RESULTS: Expressed as the percentage of total fatty acids, geometric mean concentrations of EPA, DHA, and their combination in plasma phospholipids were 1.99%, 4.52%, and 6.83%, respectively. n-3 Fatty acids were positively associated with HDL-cholesterol concentrations and inversely associated with triacylglycerol concentrations and the ratio of total to HDL cholesterol. In contrast, concentrations of total cholesterol, LDL cholesterol, and plasma glucose increased as n-3 fatty acid concentrations increased. There were no significant associations between n-3 fatty acids and diastolic and systolic blood pressure and plasma insulin. CONCLUSIONS: Consumption of marine products, the main source of EPA and DHA, appears to beneficially affect some cardiovascular disease risk factors. The traditional Inuit diet, which is rich in n-3 fatty acids, is probably responsible for the low mortality rate from ischemic heart disease in this population.

Adult↗

Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers.

BACKGROUND: Epidemiologic evidence shows an inverse relation between fish consumption and death from ischemic heart disease. This beneficial effect is attributed to n-3 fatty acids. OBJECTIVES: The purpose of this study was to examine the association between plasma phospholipid concentrations of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and various cardiovascular disease risk factors among Quebecers. DESIGN: The study population consisted of 1460 subjects aged 18-74 y who participated in the 1990 Quebec Heart Health and Nutrition Survey. Data were obtained through home interviews and clinic visits. RESULTS: Expressed as the percentage of total fatty acids in plasma phospholipids, the geometric means of EPA, DHA, and their combination were 0.47%, 1.19%, and 1.70%, respectively. Concentrations of n-3 fatty acids were positively associated with fish intake. We found positive associations between EPA and total cholesterol, LDL cholesterol, HDL cholesterol, plasma glucose, and systolic and diastolic blood pressure. We found positive associations between DHA and total cholesterol, the ratio of total to HDL cholesterol, triacylglycerols, systolic blood pressure, and plasma glucose and insulin. We also found positive associations between the ratio of EPA to arachidonic acid and total cholesterol, HDL cholesterol, and systolic blood pressure and a negative association with the ratio of total to HDL cholesterol. CONCLUSIONS: Our results indicate that concentrations of EPA and DHA in plasma phospholipids reflected Quebecer fish consumption. Results also show that EPA and the ratio of EPA to arachidonic acid can positively influence HDL-cholesterol concentrations.

Adult↗

Contribution of visceral obesity to the insulin resistance syndrome.

A high visceral adipose tissue accumulation has been associated with many metabolic perturbations typical of the insulin resistance syndrome, such as dyslipidemia, impaired glucose-insulin homeostasis, hypertension and impaired fibrinolysis. It has been documented that male gender aging, and a hyperglycemic state are conditions that increase the likelihood of displaying features of the insulin resistance syndrome. Accordingly, studies have demonstrated that the variation in visceral adipose tissue accumulation explains a significant proportion of the gender differences in the metabolic risk profile. Age-related differences in metabolic components of the insulin resistance syndrome have also been shown to be partly explained by the concomitant increase in visceral adipose tissue accumulation found with age. Studies have suggested that a high visceral adipose tissue accumulation contributes significantly to the deterioration in the plasma lipid-lipoprotein profile found in hyperglycemic subjects. Finally, it appears that the clustering of metabolic alterations of the insulin resistance syndrome is more pronounced in obese subjects with high levels of visceral fat that in those with a lower visceral adipose tissue accumulation.

Adipose Tissue↗

A genome-wide scan for abdominal fat assessed by computed tomography in the Québec Family Study.

To identify chromosomal regions harboring genes influencing the propensity to store fat in the abdominal area, a genome-wide scan for abdominal fat was performed in the Quebec Family Study. Cross-sectional areas of the amount of abdominal total fat (ATF) and abdominal visceral fat (AVF) were assessed from a computed tomography scan taken at L4-L5 in 521 adult subjects. Abdominal subcutaneous fat (ASF) was obtained by computing the difference between ATF and AVF. The abdominal fat phenotypes were adjusted for age and sex effects as well as for total amount of body fat (kilogram of fat mass) measured by underwater weighing, and the adjusted phenotypes were used in linkage analyses. A total of 293 microsatellite markers spanning the 22 autosomal chromosomes were typed. The average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were available for single-point (SIBPAL) and 156 families for multipoint variance components (SEGPATH) linkage analyses. The strongest evidence of linkage was found on chromosome 12q24.3 between marker D12S2078 and ASF (logarithm of odds [LOD] = 2.88). Another marker (D12S1045) located within 2 cM of D12S2078 also provided evidence of sib-pair linkage with ASF (P = 0.019), ATF (P = 0.015), and AVF (P = 0.0007). Other regions with highly suggestive evidence (P < 0.0023 or LOD > or =1.75) of multipoint linkage and evidence (P < 0.05) of single-point linkage, all for ASF, included chromosomes 1p11.2, 4q32.1, 9q22.1, 12q22-q23, and 17q21.1. Three of these loci (1p11.2, 9q22.1, and 17q21.1) are close to genes involved in the regulation of sex steroid levels, whereas two others (4q32.1 and 17q21.1) are in the proximity of genes involved in the regulation of food intake. This first genome-wide scan for abdominal fat assessed by computed tomography indicates that there may be several loci determining the propensity to store fat in the abdominal depot and that some of these loci may influence the development of diabetes in obese subjects.

Adipose Tissue↗

Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects.

The reason for the 3- to 4-h delay between a rise in plasma free fatty acid (FFA) levels and the development of insulin resistance remains unknown. In the current study, we have tested the hypothesis that the delay may be caused by the need for plasma FFAs to first enter muscle cells and to be re-esterified there before causing insulin resistance. To this end, we have determined intramyocellular triglyceride (IMCL-TG) content with proton nuclear magnetic resonance ((1)H-NMR) spectroscopy in healthy volunteers before and 4 h after lowering of plasma FFAs (with euglycemic-hyperinsulinemic clamping) or after increasing plasma FFAs (with lipid plus heparin infusions). Increasing plasma FFAs (from 516 to 1,207 micromol/l or from 464 to 1,857 micromol/l, respectively) was associated with acute increases in IMCL-TG from 100 to 109 +/- 5% (P < 0.05) or to 133 +/- 11% (P < 0.01), respectively, and with a significant increase in insulin resistance (P < 0.05 after 3.5 h). Lowering of plasma FFAs from 560 to 41 micromol/l was associated with a tendency for IMCL-TG to decrease (from 100 to 95 +/- 3%). Changes in plasma FFAs correlated linearly with IMCL-TG (r = 0.74, P < 0.003). The demonstration that acute changes in plasma FFAs were accompanied by corresponding changes in IMCL-TG and with the development of insulin resistance, taken together with previous reports of a close correlation between IMCL-TG and insulin resistance, supported the notion that accumulation of IMCL-TG is a step in the development of FFA-induced insulin resistance.

Adipose Tissue↗

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.

Adipose Tissue↗