Biomedical subjects

A Nadeau

Publications and source records attributed to A Nadeau.

At least 37 records · Page 2Linked to original sources

PubMed2000

Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia.

OBJECTIVES: To investigate the relationships of fat cell weight (FCW) as well as of estimated total adipose cell number to fasting plasma leptin concentration. DESIGN: Cross-sectional correlational study. SUBJECTS: A sample of 63 men (mean age+/-s.d.: 36+/-4 y) and 42 premenopausal women (35+/-5 y). MEASUREMENTS: Adipose tissue (AT) biopsies were obtained in order to determine FCW as well as estimated adipose cell number. Fasting plasma leptin and insulin concentrations as well as various fatness and body fat distribution variables (underwater weighing and computed tomography) were also measured. RESULTS: In both genders, mean FCW as well as the estimated adipose cell number were significantly correlated with body fatness and AT distribution variables (0.41</=r</=0.84). Larger abdominal (P<0.005) and femoral (P<0.0001) FCW were found in women than in men. This gender difference in adipose cell size was associated with increased leptin concentrations in women compared with men. In both genders, increased abdominal FCW was associated with higher plasma leptin concentrations (men: r=0.38, P<0.005 and women: r=0.55, P<0.0001). However, the association between femoral FCW and leptinemia was only significant in women (r=0.45, P<0.005). Contrary to women, plasma leptin concentrations were associated with estimated adipose cell number in men (r=0.59, P<0.0001). Multiple regression analyses revealed that gender (43.3%), mean FCW (16.2%) and the estimated adipose cell number (10.1%) were significant predictors of fasting leptinemia. CONCLUSIONS: Results of the present study indicate that in men and women, adipose cell hypertrophy is associated with increased plasma leptin concentrations. This finding provides further support to the observation that adipose tissue leptin secretion may be regulated, at least to a certain extent, by adipocyte size. Thus, the present study suggests that the higher plasma leptin concentrations found in women than in men could be partly explained by the well documented gender difference in adipose cell size and number.

Adipocytes↗

PubMed2000

The mixed lineage kinase leucine-zipper protein kinase exhibits a differentiation-associated localization in normal human skin and induces keratinocyte differentiation upon overexpression.

Leucine-zipper protein kinase/dual leucine zipper bearing kinase/mitogen-activated protein kinase-upstream kinase is a recently described protein serine/threonine kinase which belongs to the mixed lineage kinase family. The overall pattern of expression of the leucine-zipper protein kinase/dual leucine zipper bearing kinase/mitogen-activated protein kinase-upstream kinase gene in embryonic and adult mouse tissues suggested that this kinase could be involved in the regulation of epithelial cell proliferation and differentiation. In order to get more insights into the potential role of leucine-zipper protein kinase in these cellular processes, we characterized its expression in normal human skin, both at the mRNA and protein levels. In situ hybridization, western blotting, and indirect immunofluorescence studies were conducted to localize leucine-zipper protein kinase on various human skin tissues. This is one of the first reports that leucine-zipper protein kinase has a very precise pattern of expression in human skin epithelia, as both mRNA and protein are restricted to the granular layer of the epidermis and inner root sheath of hair follicles. Detection of leucine-zipper protein kinase protein on skin from various body sites, donors of different ages as well as on reconstructed human skin always reveals that leucine-zipper protein kinase is present only in the very differentiated keratinocytes of epidermis and hair follicles. To determine directly whether leucine-zipper protein kinase exhibits any effect on cell growth and differentiation, keratinocytes were transfected with an expression vector harboring the leucine-zipper protein kinase cDNA. The presence of this construct in keratinocytes results in growth arrest together with a concomitant increase in filaggrin expression. Collectively, our results indicate that leucine-zipper protein kinase plays an active part in cellular processes related to terminal differentiation of epidermal keratinocytes.

Adolescent↗

PubMed2000

Effect of metformin on the vascular and glucose metabolic actions of insulin in hypertensive rats.

We investigated the long-term effect of metformin treatment on blood pressure, insulin sensitivity, and vascular responses to insulin in conscious spontaneously hypertensive rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and blood flow. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Two groups of SHR received metformin (100 or 300 mg x kg(-1) x day(-1)) for 3 wk while another group of SHR and a group of Wistar Kyoto (WKY) rats were left untreated. We found that vasodilation of skeletal muscle and renal vasculatures by insulin is impaired in SHR. Moreover, a reduced insulin sensitivity was detected in vivo and in vitro in isolated soleus and extensor digitorum longus muscles from SHR compared with WKY rats. Three weeks of treatment with metformin improves the whole-body insulin-mediated glucose disposal in SHR but has no blood pressure-lowering effect and no influence on vascular responses to insulin (4 mU x kg(-1) x min(-1)). An improvement in insulin-mediated glucose transport activity was detected in isolated muscles from metformin-treated SHR, but in the absence of insulin no changes in basal glucose transport activity were observed. It is suggested that part of the beneficial effect of metformin on insulin resistance results from a potentiation of the hormone-stimulating effect on glucose transport in peripheral tissues (mainly skeletal muscle). The results argue against a significant antihypertensive or vascular effect of metformin in SHR.

Animals↗

PubMed2000

Subcutaneous adipose tissue metabolism at menopause: importance of body fatness and regional fat distribution.

The aim of this study was to examine the contribution of menopause per se on sc adipose tissue (AT) metabolism in 16 women classified on the basis of their menopausal status: 8 postmenopausal (mean +/- SD age, 57 +/- 6 yr) vs. 8 premenopausal individuals (37 +/- 5 yr). These 2 groups were matched for sc abdominal adipose cell size (within 0.02 microg lipid/cell) and visceral AT accumulation (within 15 cm2), measured by computed tomography. Fasting plasma glucose and insulin levels as well as their responses to an oral glucose load were similar regardless of the women's hormonal status. Subcutaneous abdominal and femoral AT lipoprotein lipase activities as well as fat cell lipolysis were determined in both groups. Epinephrine induced antilipolysis at low concentrations and lipolysis at higher doses in both adipose sites and groups. The maximal lipolytic response to epinephrine or to isoproterenol (beta-adrenergic agonist) as well as the maximal antilipolytic effect of either the catecholamine or UK-14304 (alpha2-adrenergic agonist) assessed in sc adipocytes were similar in pre- and postmenopausal women. In addition, neither the beta- nor the alpha2-adrenoceptor sensitivity of sc adipose cells differed according to subjects' age. Finally, maximal lipolysis promoted by postadrenoceptor agents and AT-lipoprotein lipase activity did not vary among adipose regions or between groups. Taken together, these results suggest that menopause per se does not influence sc AT metabolism once the variation related to adipose cell size and total body fatness is taken into account.

Adipocytes↗

PubMed2000

Impact of time interval from the last meal on glucose response to exercise in subjects with type 2 diabetes.

We evaluate the influence of the time interval from the last meal on the blood glucose response to exercise in men with type 2 diabetes. Nineteen men with type 2 diabetes participated in an exercise training program carried out at 60% of maximal oxygen uptake (VO2peak) for 1 h, 3 times a week. Capillary whole blood glucose was measured immediately before and after each exercise session, and the time interval from the last meal (breakfast, lunch, or dinner) was recorded. Seven time intervals were considered (fasted overnight and 0-1, 1-2, 2-3, 3-4, 4-5, and 5-8 h postmeal). A total of 1,045 exercise sessions were analyzed. There was no change in blood glucose levels when individuals were in the fasted state (mean +/- SE, 8.1 +/- 0.2 vs. 8.1 +/- 0.1 mmol/L; before vs. after, respectively). However, blood glucose decreased by 28 +/- 1% at 0-1 h, by 33 +/- 1% at 1-2 h, by 35 +/- 1% at 2-3 h, by 38 +/- 2% at 3-4 h, by 43 +/- 2% at 4-5 h, and by 23 +/- 3% at 5-8 h (all P < 0.001). These results demonstrate that 1 h of ergocycle exercise has no clinical impact on blood glucose when performed in the fasted state in men with type 2 diabetes, whereas a significant decrease in blood glucose should be expected when the same exercise is performed postprandially.

Adult↗

PubMed1999

Evidence of a major locus for lipoprotein lipase (LPL) activity in addition to a pleiotropic locus for both LPL and fasting insulin: results from the HERITAGE Family Study.

A major gene hypothesis for heparin releasable plasma lipoprotein lipase (PH-LPL) activity was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of Caucasian descent who participated in the HERITAGE Family Study. Segregation analyses were performed on PH-LPL adjusted for age, and on PH-LPL activity adjusted for age and fasting insulin. Prior to adjustment for insulin, neither a major gene effect nor a multifactorial component could be rejected, and support for a major gene was equivocal i.e. neither the Mendelian transmission nor the no transmission (equal tau s) models were rejected. However, after adjusting for the effects of insulin, a major gene effect on PH-LPL activity was unambiguous. The putative locus accounted for 60% of the total phenotypic variance, and the homozygous recessive form affected 10% (q2) of the sample (i.e. gene frequency (q) = 0.31), and led to a low PH-LPL value. The lack of a significant multifactorial effect suggested that the familial etiology of PH-LPL activity adjusted for insulin was likely to be primarily a function of the major locus. In conclusion, the present study is the first to report segregation analyses on PH-LPL activity prior to and after adjusting for insulin, and suggests that there is an indication of a pleiotropic genetic effect on PH-LPL activity and insulin, in addition to a major gene effect on PH-LPL activity alone.

Adolescent↗

PubMed1999

Relationship of visceral adipose tissue to metabolic risk factors for coronary heart disease: is there a contribution of subcutaneous fat cell hypertrophy?

Visceral adipose tissue (VAT) accumulation is an important correlate of the metabolic complications found in obese patients. The aim of this study was to evaluate the respective contribution of VAT deposition versus subcutaneous abdominal or femoral fat cell hypertrophy as correlates of the metabolic risk profile in 69 men and 65 premenopausal women (aged 35+/-5 years) with a wide range of fatness (body mass index, 18 to 57 kg/m2). In both genders, VAT accumulation was positively correlated with fasting plasma insulin, triglyceride (TG), and low-density lipoprotein (LDL)-apolipoprotein B (apo B) levels and the cholesterol (CHOL)/high-density lipoprotein (HDL)-CHOL ratio (.24 < or = r < or = .71, P < .05). A similar pattern of positive relationships was found between subcutaneous abdominal fat cell weight and metabolic risk variables in men and women (.33 < or = r < or = .60, P < .01). Positive associations were also observed in women between femoral fat cell weight and fasting plasma insulin, TG, and CHOL levels and the CHOL/HDL-CHOL ratio (.29 < or = r < or = .42, P < .05). However, only plasma TG concentrations and the CHOL/HDL-CHOL ratio were positively correlated with femoral fat cell weight in men (r = .30, P < .05). To better investigate the relationships between the metabolic risk profile and hypertrophic subcutaneous obesity, individuals with small versus large subcutaneous abdominal adipocytes were matched according to VAT accumulation. Men with large abdominal fat cells displayed higher plasma TG and LDL-apo B levels compared with men characterized by small abdominal adipocytes (P < .05). Stepwise multiple regression analyses showed that subcutaneous abdominal fat cell weight was the best independent variable predicting plasma TG and LDL-apo B levels in men. No significant difference was found in the metabolic profile of subjects displaying small versus large femoral adipocytes. Taken together, these results suggest that for a given VAT deposition, the presence of hypertrophied subcutaneous abdominal adipocytes in men appears to be associated with further deterioration in the metabolic risk profile. On the other hand, the hypertrophy of femoral adipocytes does not further alter the metabolic complications generally related to obesity in both men and women.

Adipocytes↗

PubMed1999

Plasma adrenal, gonadal, and conjugated steroids following long-term exercise-induced negative energy balance in identical twins.

There are few reports of the change in sex hormone levels accompanying a weight change in men, although an excessive decline in testosterone (TESTO) has been described as an associate of stress-induced weight loss. Plasma levels of cortisol, TESTO, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), androsterone glucuronide (ADT-G), and androstane-3alpha, 17beta-diol glucuronide (3alphaDIOL-G) were measured in seven pairs of sedentary male monozygotic twins (age, 21.0 +/- 0.8 years; body mass index [BMI], 26.2 +/- 5.5 kg/m2) before and after 93 days of standardized submaximal (50% to 55% maximum oxygen consumption) cycle-ergometer exercise. A total energy deficit of 244 +/- 9.7 MJ induced significant changes (P < .0001) in body weight ([BW] -5.0 +/- 2.2 kg) and body fatness measures. Plasma TESTO and DHEA-S increased and 3alphaDIOL-G decreased. The increase in TESTO was a significant inverse correlate of loss in all measures of body fat, particularly central adiposity (r = -.58 to -.86, P < .001, fat loss-adjusted). Lower postexercise levels of 3alphaDIOL-G correlated positively with decreased body composition measures (r = .65 to .68, P < .01). The increase in plasma TESTO accompanying the loss of abdominal visceral fat (AVF) was greater in men with lower fasting insulin levels (P < .0001). The baseline within-twin-pair resemblance in TESTO and 3alphaDIOL-G (intraclass correlation coefficients [ICC] = .83 and .78, respectively, P < .01) was lost with intervention. Cortisol, DHEA-S, and ADT-G developed within-twin-pair similarity (ICC adjusted for fat loss: cortisol, .72; ADT-G, .62, P < .05; DHEA-S, .85, P < .002). We conclude that a steroid profile characterized by high TESTO and low androgen metabolite levels accompanied the changes in body composition and body fat distribution generated by the exercise-induced negative energy balance. Furthermore, these changes were characterized by a significant resemblance within identical-twin pairs.

Adult↗

PubMed1999

Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome.

OBJECTIVE: The aim of this study was to examine the relation between the CETP-TaqIB polymorphism and reduced plasma HDL-cholesterol levels commonly observed among men characterized by abdominal obesity and features of the insulin resistance syndrome. SUBJECTS: A total of 187 sedentary men, non-smokers and free from metabolic disorders were classified on the basis of their CETP-TaqIB genotype. RESULTS: Plasma HDL and HDL3-cholesterol concentrations as well as the CETP activity were significantly different between the three genotypes, B1B1 men having significantly lower HDL and HDL3-cholesterol levels and higher CETP activity than B2B2 homozygotes. A 2x3 ANOVA was used to determine the source of variation of plasma HDL and HDL2-cholesterol levels among the three genotypic groups of men divided on the basis of either a high (>/=27 kg/m2) or a low (<27 kg/m2) BMI, a high (>/=130 cm2) or a low (<130 cm2) accumulation of visceral adipose tissue assessed by computed tomography, or a low versus a high fasting plasma insulin concentration (using the median value as a cut-off point). The effect of the CETP genotype observed on plasma HDL-cholesterol concentrations was attenuated among men with features of the insulin resistance syndrome. It seems that the expected raising effect of the B2 allele on plasma HDL-cholesterol concentrations was blunted in the presence of a BMI>/=27 kg/m2, a high accumulation of visceral adipose tissue or hyperinsulinaemia. CONCLUSION: Our data indicate that the CETP gene TaqIB polymorphism influences plasma CETP activity on one hand and plasma HDL-cholesterol concentrations on the other hand among men. The association between the TaqIB polymorphism and plasma HDL-cholesterol concentrations is altered by the presence of abdominal obesity and some features of the insulin resistance syndrome.

Abdomen↗

PubMed1999

Linkage of the Na,K-ATPase alpha 2 and beta 1 genes with resting and exercise heart rate and blood pressure: cross-sectional and longitudinal observations from the Quebec Family Study.

OBJECTIVE: To investigate whether genetic variations in the genes encoding the alpha and beta subunits of the Na,K-ATPase are linked with hemodynamic phenotypes. DESIGN AND PARTICIPANTS: Cross-sectional data based on 533 subjects (no antihypertensive medication) were obtained from 150 families of phase 2 of the Quebec Family Study, together with longitudinal data from 338 subjects (105 families) who had been measured 12 years earlier in phase 1 of the Quebec Family Study. MAIN OUTCOME MEASURES: Restriction fragment length polymorphisms were examined at the alpha 2 (exon 1 and exon 21-22 with BglII) and beta 1 (Msp I and Pvu II) loci of Na,K-ATPase. Hemodynamic phenotypes measured included systolic and diastolic blood pressure, heart rate and rate-pressure product at rest and during low-intensity exercise. RESULTS: Sib-pair analysis revealed relatively strong linkages (P = 0.0003-0.002) between the resting heart rate and rate-pressure product and the alpha 2 exon 21-22 marker and alpha 2 haplotype. Moreover, the alpha 2 exon 21-22 marker showed suggestive linkages (P = 0.01 to 0.043) with resting systolic blood pressure and exercise diastolic blood pressure, heart rate and rate-pressure product, and the alpha 2 haplotype with exercise diastolic blood pressure and rate-pressure product and the 12-year change in resting systolic blood pressure (P = 0.03 to 0.05). Both the beta 1 Msp I marker and the beta 1 haplotype were linked with the resting rate-pressure product (P = 0.007 and 0.003, respectively), and all beta 1 markers showed linkage with the change in resting systolic blood pressure (P = 0.00005 to 0.024). In men, there was a significant (P = 0.01) interaction between the alpha 2 exon 21-22 genotype and the postglucose plasma insulin level with regard to resting systolic blood pressure. CONCLUSIONS: These data suggest that the alpha 2 and beta 1 genes of Na,K-ATPase contribute to the regulation of hemodynamic phenotypes in healthy subjects.

Blood Pressure↗

PubMed1999

Apolipoprotein E polymorphism and the relationships of physical fitness to plasma lipoprotein-lipid levels in men and women.

PURPOSE: A high level of cardiovascular fitness is generally associated with a plasma lipoprotein-lipid profile predictive of a low cardiovascular disease risk. We have investigated whether apolipoprotein (apo) E polymorphism could alter the relationships of physical fitness to plasma lipoprotein-lipid levels in a sample of healthy untrained subjects (64 premenopausal women and 65 men). METHODS: Subjects were grouped according to gender and apo E phenotype determined by isoelectric focusing electrophoresis. RESULTS: In both genders, VO2max expressed in mL x kg(-1) x min(-1) was negatively correlated with plasma triglyceride levels in apo E2 carriers and apo E3 homozygotes (-0.55< or =r< or =0.31; P<0.05), whereas these associations were not found in apo E4 groups. Plasma low-density lipoprotein (LDL)-C levels were negatively associated with VO2max (r = -0.39; P<0.05) only in women homozygotes for apo E3 whereas VO2max was positively correlated with plasma high-density lipoprotein (HDL)2-C levels only in men (r = 0.51; P<0.001) and women (r = 0.65; P<0.001) who were apo E3 homozygotes. A control for concomitant association with body fat mass and glucose intolerance performed by partial correlation analyses revealed that, with the exception of the plasma HDL2-C levels in the apo E3 homozygotes, most of the significant associations between VO2max (mL x kg(-1) x min(-1)) and plasma lipoprotein-lipid levels were mediated by concomitant variation in body fatness and glucose tolerance. CONCLUSIONS: These results suggest that the magnitude of the relationships between VO2max and plasma lipoprotein-lipid levels is influenced by the apo E polymorphism. Thus, apo E2 carriers may be particularly responsive to improved fitness, thereby preventing the development of hypertriglyceridemia and type III dyslipoproteinemia.

Adult↗

PubMed1999

Isradipine and insulin sensitivity in hypertensive rats.

The present study was designed to investigate the effect of a reduction in blood pressure, by using the calcium channel antagonist isradipine, on insulin sensitivity and vascular responses to insulin in conscious spontaneously hypertensive male rats (SHR). The rats were instrumented with intravascular catheters and pulsed Doppler flow probes to measure blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp technique. Two groups of rats received isradipine at a dose of 0.05 or 0.15 mg. kg-1. h-1, whereas a third group received a continuous infusion of vehicle (15% DMSO). Both doses of isradipine were found to decrease mean blood pressure (-25 +/- 4 mmHg at the dose of 0.05 mg. kg-1. h-1 and -20 +/- 2 mmHg at the dose of 0.15 mg. kg-1. h-1) and to improve insulin sensitivity. Moreover, in the rats treated with the low dose of isradipine, we observed vasodilations in renal, superior mesenteric, and hindquarter vascular beds. In the untreated group, the euglycemic infusion of insulin (4 mU. kg-1. min-1) was found to cause vasoconstrictions in superior mesenteric and hindquarter vascular beds, but no changes in mean blood pressure, heart rate, or renal vascular conductance were found. In contrast, in the isradipine-treated groups, the same dose of insulin was found to produce vasodilations in the renal vascular bed and to abolish the vasoconstrictor responses previously observed. We concluded that short-term treatment with isradipine in SHR can lower blood pressure and improve insulin sensitivity, mainly through hemodynamic factors, as supported by experiments with hydralazine as a positive vasodilator control.

Animals↗

PubMed1999

Is visceral adiposity a significant correlate of subcutaneous adipose cell lipolysis in men?

The aim of the present study was to examine whether site differences in s.c. adipose tissue (AT) lipolysis may be considered a contributing factor to the altered metabolic risk profile of visceral compared to peripheral obese men once the concomitant variation in adipose cell size is taken into account. For this purpose, sc abdominal and femoral fat cell lipolytic responses were investigated in two groups of men (body mass index, 28 +/- 2 kg/m2), aged 36 +/- 3 yr, who were matched for both s.c. abdominal AT area (256 +/- 64 cm2) and s.c. abdominal adipose cell weight (0.55 +/- 0.08 microg lipid/cell) but were characterized by either a high (162 +/- 29 cm2; n = 18) or a low (101 +/- 21 cm2; n = 18) visceral AT deposition. The maximal lipolytic response to epinephrine or to isoproterenol (beta-adrenergic agonist) as well as the maximal antilipolytic effect of either epinephrine or clonidine (alpha2-adrenergic agonist) assessed in s.c. adipocytes were similar among men with low vs. high levels of visceral AT. However, the beta-adrenoceptor sensitivity was increased in s.c. abdominal adipose cells of individuals with a high visceral AT accumulation compared to those with a low intraabdominal fat deposition. Positive relationships were also found between the lipolytic sensitivity of s.c. abdominal adipocytes and plasma insulin concentrations measured in the fasting state and after an oral glucose load. These results suggest that variation in the degree of visceral adiposity in men does not seem to be associated with differences in regional adipose cell maximal lipolytic capacity once fat cell size is taken into account. However, the greater beta-adrenoceptor lipolytic sensitivity of s.c. abdominal adipocytes could be considered a significant correlate of the increased insulinemia observed among men characterized by high levels of visceral AT.

Abdomen↗

PubMed1999

Age-related increase in visceral adipose tissue and body fat and the metabolic risk profile of premenopausal women.

OBJECTIVE: Age-related differences in body fat and, more specifically, in the accumulation of abdominal visceral adipose tissue (AT) were examined as potential covariates of the age-related difference in the metabolic profile predictive of cardiovascular disease (CVD) risk observed in young, as compared with middle-aged, premenopausal women. RESEARCH DESIGN AND METHODS: Body composition, AT distribution, plasma lipoprotein-lipid levels, glucose tolerance, and plasma insulin concentrations were assessed in a sample of 122 young women (27.4+/-7.5 years, mean +/- SD) and compared with a sample of 52 middle-aged premenopausal women (49.5+/-5.3 years) who still had a normal menstrual cycle. RESULTS: Middle-aged women were characterized by elevated levels of total abdominal and visceral AT and greater body fat mass and waist circumference, as well as by higher plasma levels of total cholesterol, LDL cholesterol, apolipoprotein (apo)B, and LDL-apoB compared with younger women. Furthermore, middle-aged women showed a greater glycemic response to a 75-g oral glucose load than young women (P < 0.01). In both young and middle-aged subjects, visceral AT accumulation was significantly correlated with plasma triglyceride, apoB, and LDL-apoB levels and with the cholesterol/HDL cholesterol ratio, as well as with plasma glucose, insulin, and C-peptide levels measured in the fasting state and after the oral glucose load, and negatively correlated with HDL cholesterol levels (-0.41 < or = r < or = 0.65, P < 0.05). When variables were adjusted for levels of visceral AT and fat mass, age-related differences that were initially found in plasma apoB and LDL-apoB levels, as well as in fasting glycemia and glucose tolerance, were eliminated. CONCLUSIONS: Results of the present study suggest that even before the onset of menopause there is an age-related deterioration in the metabolic risk profile and an increase in visceral AT deposition in middle-aged women compared with young control subjects. Furthermore, our results provide support for the notion that the age-related increase in visceral AT accumulation is a significant factor involved in the deterioration of the CVD risk profile noted in premenopausal women with age.

Adipose Tissue↗

PubMed1998

Familial clustering of insulin and abdominal visceral fat: the HERITAGE Family Study.

Abdominal visceral fat (AVF) is an obesity-related phenotype thought to be associated with insulin resistance, diabetes mellitus, and atherosclerosis. Significant genetic influences on both AVF and insulin levels have been reported. However, information is lacking as to whether common genetic influences on AVF and insulin levels exist. AVF was assessed by computed tomography scan, and fasting insulin was measured by RIA in 512 members of 98 sedentary Caucasian families participating in the HERITAGE Family Study. Baseline data, collected before exercise training, were used in the present investigation. A bivariate familial correlation model was applied to evaluate whether there are familial influences that are common to insulin and AVF before and after adjustment for total fat mass (FM), and to assess the overall heritability of insulin and AVF. The maximal heritability for AVF, before and after adjustment for total FM, was 42% and 50%, respectively; and for insulin, it was 21%. Interestingly, 29% of the familial influences on insulin were also common to AVF, whereas 14% of the familial influences on AVF were shared by insulin. Furthermore, after AVF was adjusted for total FM, these common familial influences were increased to 48% and 20%. Genes and/or familial nongenetic factors with pleiotropic effects seem to influence both AVF and plasma insulin levels to a certain degree. Genes involved in the regulation of lipid storage and mobilization in the abdominal fat depot are potential candidates for these genetic pleiotropic effects.

Adipose Tissue↗

PubMed1998

Plasma adrenal, gonadal, and conjugated steroids before and after long-term overfeeding in identical twins.

An analysis of the data collected in the Quebec Overfeeding Study of identical twins was undertaken to determine any evidence of a genotype effect on plasma levels of adrenal and gonadal steroids arising from long term positive energy balance. Plasma levels of sex hormone-binding globulin (SHBG), testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), androsterone glucuronide, androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-DIOL-G), and cortisol were measured in 12 pairs of young, sedentary, male monozygotic twins before and after 100 days of overfeeding. The dietary energy excess of 4.2 MJ/day (1000 Cal), 6 days a week, resulted in a total positive energy balance of 353 MJ (84,000 Cal). Overfeeding induced significant changes (P < 0.0001) in body weight and other measures of body composition. Within-twin pair resemblance was observed at baseline in all steroids, except cortisol [intraclass correlation range: DHEA-S, 0.50 (P < 0.05); DHT, 0.77 (P < 0.001)] and was lost with overfeeding, except for DHT and SHBG (P < 0.05). SHBG levels fell and 3 alpha-DIOL-G rose with the gain in body fatness. The change in testosterone was a significant correlate of the change in upper body fat (r = -0.48; P < 0.05). The change in 3 alpha-DIOL-G correlated positively with increases in all measures of central adiposity (r = 0.52; P < 0.01). A decrease in DHEA-S occurred with a higher, but not with a lower, gain in abdominal visceral fat (P < 0.05). Thus, analysis of adrenal and gonadal steroids and of conjugated metabolites before and after overfeeding in monozygous twins supports the idea that there is a genotype effect on steroid circulating steroid levels and that these blood levels are correlated with the pattern of body fat distribution. Moreover, the baseline within-twin pairs similarity in steroid levels was attenuated by prolonged positive energy balance and body fat gain.

Adipose Tissue↗

PubMed1997

Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q.

Chromosomal synteny between the mouse model and humans was used to map a gene for the complex trait of obesity. Analysis of NZB/BINJ x SM/J intercross mice located a quantitative trait locus (QTL) for obesity on distal mouse chromosome 2, in a region syntenic with a large region of human chromosome 20, showing linkage to percent body fat (likelihood of the odds [LOD] score 3.6) and fat mass (LOD score 4.3). The QTL was confirmed in a congenic mouse strain. To test whether the QTL contributes to human obesity, we studied linkage between markers located within a 52-cM region extending from 20p12 to 20q13.3 and measures of obesity in 650 French Canadian subjects from 152 pedigrees participating in the Quebec Family Study. Sib-pair analysis based on a maximum of 258 sib pairs revealed suggestive linkages between the percentage of body fat (P < 0.004), body mass index (P < 0.008), and fasting insulin (P < 0.0005) and a locus extending approximately from ADA (the adenosine deaminase gene) to MC3R (the melanocortin 3 receptor gene). These data provide evidence that a locus on human chromosome 20q contributes to body fat and insulin in a human population, and demonstrate the utility of using interspecies syntenic relationships to find relevant disease loci in humans.

Adipose Tissue↗

PubMed1997

The MspI polymorphism of the apolipoprotein A-II gene as a modulator of the dyslipidemic state found in visceral obesity.

The aim of the present study was to examine the effect of variation at the apolipoprotein (apo) A-II gene locus on lipoprotein levels in visceral obesity. A total of 145 sedentary men, free from metabolic disorders requiring pharmacotherapy, were classified into two groups on the basis of their apo A-II-MspI genotype determined by the polymerase chain reaction: 1) 43 M1 carriers or M1M2, including two M1M1 homozygotes and 41 M1M2 heterozygotes, and 2) 102 M2M2 homozygotes for the presence of a MspI restriction site. The two genotypic groups did not differ for body mass index (BMI, expressed in kg/m2), body fat mass, visceral adipose tissue (AT) accumulation, as well as for insulin, glucose and free fatty acids levels measured in the fasting state and in response to an oral glucose tolerance test. In addition, 65 and 63% of M1 carriers had plasma HDL2 cholesterol levels and a HDL2/HDL3 cholesterol ratio below the 50th percentile of their distributions compared with 45%(P < 0.05) and 46%(P = 0.06), respectively, in M2M2 homozygotes. When subjects were further divided on the basis of visceral AT accumulation (below and above a value of 130 cm2), M1 carriers with low levels of visceral AT were characterized by high plasma HDL cholesterol and HDL2 cholesterol concentrations as well as by a higher HDL2/HDL3 ratio, compared with M1 carriers with high levels of visceral AT (> 130 cm2), or with M2M2 homozygotes with either a high or a low accumulation of visceral AT. Furthermore, M1 carriers with high levels of visceral AT showed a trend for lower plasma HDL2 cholesterol levels and were characterized by a significantly lower HDL2/HDL3 cholesterol ratio compared with the other three groups. No difference in HDL and HDL2 cholesterol levels and in the HDL2/HDL3 cholesterol ratio was noted when M2 homozygotes with lower versus higher levels of visceral AT were compared. The contribution of hyperinsulinemia was also examined by dividing subjects on the basis of the 50th percentile of the integrated insulin response to an oral glucose challenge. Significantly lower plasma HDL2 cholesterol levels and a reduced HDL2/HDL3 cholesterol ratio were noted among M1 carriers with high plasma insulin responses compared with M1 carriers with low insulin responses. Among M2M2 homozygotes, no difference was noted in plasma HDL cholesterol and in HDL2 cholesterol concentrations between men with low versus high insulin responses to the oral glucose load. These results suggest that the apo A-II-MspI polymorphism could modulate plasma HDL cholesterol levels among visceral obese, insulin-resistant men.

Adipose Tissue↗