Publications

An Exploratory Investigation of Genetic Linkage with Body Composition and Fatness Phenotypes: The Québec Family Study

In the present investigation, we have attempted to identify regions of the genome in which “obesity genes” potentially reside using robust sib‐pair linkage analysis. Data were collected on 1,628 individuals in 301 nuclear families residing in the environs of Québec City during the period 1978–1981. In addition to traditional blood group antigens and enzyme polymorphisms, several phenotypes in the obesity domain that are associated with increased morbidity were assessed, including measures relating to heaviness (i.e., the body mass index), body composition and nutrient partitioning (i.e., % body fat), and regional fat distribution without and with standardization for total fat mass (i.e., the sum of six skinfold thicknesses, and the ratio of the sums of trunk to extremity skinfold thicknesses). Three consistent patterns of potential linkage relationships with obesity phenotypes were revealed in these data, involving the marker loci adenosine deaminase, the Kell blood group antigen, and esterase D, which identify chromosomal regions 20q13, 7q33, and 13q14, respectively. Other potential linkages also were identified in the short arm of chromosome 1, interesting because of the presence of the db and fa loci on homologous regions of chromosome 1 in mouse and rat models of obesity, respectively. Each of the tentative linkage relationships reported here warrant follow‐up using alternative methods and require replication in independent studies.

Reply to R Swaminathan

No abstract is provided for this article.

Race differences in the response of postheparin plasma lipoprotein lipase and hepatic lipase activities to endurance exercise training in men

Endurance exercise training is known to produce favorable changes in the metabolic profile including reduced plasma triglyceride (TG) and increased high-density lipoprotein (HDL) cholesterol concentrations. These metabolic improvements are likely to contribute to the reduced coronary heart disease (CHD) risk often observed in physically active individuals. However, the physiological mechanisms responsible for such improvements in TG and HDL cholesterol concentrations with endurance exercise are not fully understood. The effect of a 20-week endurance exercise training program on plasma lipoproteins as well as on post-heparin plasma lipoprotein lipase (PH-LPL) and hepatic lipase (PH-HL) activities were therefore examined in a sample of 200 White and 69 Black men who were part of the HERITAGE Family Study. As expected, there were decreases in adiposity and in abdominal fat accumulation following training in both White and Black men. We also found that exercise training was associated with decreases in plasma cholesterol, TG and apolipoprotein B levels, as well as with an increase in HDL cholesterol concentrations in White men. In contrast, Black men showed an increase only in HDL2 cholesterol over the 20-week period. Higher PH-LPL and lower PH-HL activities were noted in both ethnic groups at follow-up. Whereas in White men improvement of the lipoprotein–lipid profile was related to increased PH-LPL activity, no association between PH-LPL (or PH-HL) and lipoprotein–lipid variables was observed in Black men. Results of the present study suggest that in Whites, the increase in PH-LPL activity in response to endurance exercise training is associated with a better lipoprotein–lipid profile, therefore reducing CHD risk. However, the generally better metabolic profile of Black individuals may minimize further improvement of lipoprotein–lipid concentrations by exercise training.

Physical activity and nutrition in the context of fitness and health.

No abstract is provided for this article.

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.

Kcnc1 Gene Polymorphism Is Not Associated With Endurance Performance Level In Hispanics

A DNA sequence variant in the K+ voltage-gated channel of the shaw related subfamily member 1 (KCNC1) gene (11p15) is known to be associated with VO2max in the sedentary and trained states in Blacks, but not in Whites (MSSE 36(5), S99, 2003). PURPOSE To examine the association between the same KCNC1 gene polymorphism and endurance performance level in a cohort of Hispanics. METHODS The polymorphism was detected by PCR and digestion with MspI in 302 DNA samples from Hispanic marathon runners (n=225) and cardiac patients (n = 77). They were divided into three groups according to endurance performance level. Cases (C; n = 105) and active controls (AC; n = 120), were long-distance runners finishers in the highest and lowest 3 percentile, by age and gender respectively, during an international marathon (42 km) race, while controls (CON; n = 77) were intensive care coronary unit subjects with severely compromised cardiorespiratory functions. RESULTS The observed KCNC1 genotypic frequencies for both genders were in Hardy-Weinberg equilibrium (X2, P>0.05). X2 analysis showed that neither allelic nor genotype frequencies were significantly (P>0.05) different between genders or groups. The pooled genotypic and allelic data is shown in the table below.TableCONCLUSION The present findings do not provide support for the notion that the K+ voltage-gated channel of the shaw related subfamily member 1 is associated with endurance performance status in Hispanics. Supported by CRC-RCMI 1P20RR11126, RCMI #G12RR03051, Comite de Fondismo: FPRA, Maraton Pacifico, Maraton de Guadalajara, and Maraton Popular de Madrid.

Effects of cholesterol ester transfer protein (CETP) gene on adiposity in response to long-term overfeeding

Cholesterol ester transfer protein (CETP) plays a key role in remodeling triglyceride-rich particles and high-density lipoproteins (HDL). We investigated CETP sequence variants in response to long-term overfeeding (100 days) in 12 pairs of male monozygotic twins (mean age±S.D.: 21±2 years). Body fat mass (FM), abdominal subcutaneous (ASF) and visceral fat (AVF), and plasma lipoproteins were determined. The CETP variants C>T/In9 (rs289714) and G>A/Ex14 (rs5882, or I405V) were investigated by RFLP-PCR methodologies. Before overfeeding, the CETP CC/In9 (n =18) genotype was associated with lower FM compared to the C>T/In9 heterozygotes. Overfeeding induced more FM and ASF accretion in C>T/In9 carriers (P ≤0.05). CETP V405V homozygotes (n =8) had lower BMI, FM, and ASF before overfeeding than those with the I405I (n =6) or I405V (n =10) genotypes. However, V405V subjects had the largest gain in AVF with overfeeding (P =0.02). Decreases from baseline were significantly different across the I405V genotypes for HDL-C, HDL-Apo AI, HDL2, and HDL3 (P ≤0.05). Our data suggests that CETP sequence variation contributes to the undesirable changes in adiposity and HDL-C levels when exposed to excessive calorie consumption and may be potentially helpful to identify individuals with the metabolic syndrome who are at higher risk of cardiovascular disease.

Genetics and the metabolic syndrome.

最大運動後の心拍(数)回復はアセチルコリン受容体M2(CHRM2)遺伝子多型と関連する

No abstract is provided for this article.

EcoRI restriction fragment length polymorphism in human glycogen synthase gene

No abstract is provided for this article.

Genetic control of body weight by the human brain proteome

Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with body weight but the biological relevance of most remains unexplored. Given the critical role of the brain in multiple biological processes associated with body weight regulation, we set out to determine whether genetic variants linked with body mass index (BMI) could be mapped to brain proteins. Using genetic colocalization, we mapped 23 loci from the largest BMI GWAS (n=806,834) to brain proteins (obtained from a dataset of &gt;7000 dorsolateral prefrontal cortex proteins measured by mass spectrometry in &gt;400 individuals). We also performed a proteome-wide Mendelian randomization analysis followed by genetic colocalization, which allowed us to identify an additional 48 brain proteins linked with BMI. Multi-trait colocalization suggested that more than 75% of the protein quantitative trait loci (pQTL)-BMI associations are mediated via protein expression and not via RNA expression. Single-cell sequencing from the human brain cortex revealed that the genes expressing the proteins associated with BMI may be predominantly expressed in oligodendrocytes. In the Québec Family Study, a genetic risk score (GRS) including these brain pQTLs was associated with higher dietary carbohydrate intake and lower lipid intake whereas a GRS including the 67 variants most strongly associated with BMI was not associated with dietary intake. In conclusions, we identified 71 proteins expressed in the prefrontal cortex that may be critical regulators of body weight and possibly dietary intake in humans.

Change in sleep duration and visceral fat accumulation over 6 years in adults

To investigate the relationship between change in sleep duration and long-term visceral adiposity change in adults.A longitudinal analysis was conducted on 293 participants, aged 18-65 years, followed for a mean of 6.0 ± 0.9 years. At baseline and year 6, sleep duration was self-reported and visceral adipose tissue (VAT) assessed using computed tomography. Multivariable modeling was used to examine the association between change in sleep duration and VAT change over the 6-year time period, with adjustments made for age, sex, change in BMI, personal characteristics, energy intake, and physical activity.Participants gained an average of 19.2 ± 37.3 cm(2) in VAT over the follow-up period. Baseline short (≤6 h/day) and long (≥9 h/day) sleepers gained significantly more VAT than those reporting sleeping 7-8 hours a night (23.4 and 20.2 cm(2) vs. 14.1 cm(2) , respectively, P < 0.05). Using continuous data, we observed that the change in sleep duration was not associated with VAT change. However, a change in sleep duration from ≤6 h/day to 7-8 h/day was associated with 6 cm(2) fewer VAT gain after multivariable adjustment (P < 0.05).A spontaneous change in sleep duration (from a short to an adequate duration) is independently and inversely associated with long-term VAT accumulation.

Abstract P185: Plasma Lipidome Signature of Visceral Fat Reveals Heterogenous Cardiometabolic Risk Profiles

Background: Excessive visceral fat is associated with metabolic alterations and is a causal risk factor for CVD. The plasma lipidome is altered in obesity and lipidome signatures of BMI and obesity have been identified. However, few studies have examined the plasma lipidome in relation to visceral fat. Methods: Plasma lipids were measured using the C8-positive LC-MS method in 671 participants from the HERITAGE Family Study (56% Female, 35% Black, 35 yrs). Visceral fat was measured using CT scans. Linear mixed models were used to test the associations of 193 known plasma lipids with visceral fat adjusting for age, sex, race, and BMI. A FDR&lt;5% was used to determine significance. Results: In individual models, 156 lipid species were significantly associated with visceral fat, with 109 species associated after additional adjustment for BMI ( Fig 1 ). The top positively associated lipids were triglycerides, while cholesterol esters showed the strongest inverse associations with visceral fat. A LASSO regression model retained 73 lipids and explained 78.5% of the variance in visceral fat. Delta visceral fat was calculated as the difference between predicted (from LASSO) and measured visceral fat. Examining quartiles of delta visceral fat showed that discordance between predicted and actual visceral fat was associated with differing cardiometabolic profiles independent of age, sex, race, visceral fat, and BMI. Individuals with higher delta visceral fat (Q4, overpredicted) had significantly (p&lt;1.0x10 -04 ) higher levels of TG, apoB, total cholesterol, LDL-C, and fasting insulin and lower levels of large HDL particles and LPL activity compared to those with lower delta visceral fat (Q1, underpredicted). Conclusions: The plasma lipidome is widely associated with visceral fat levels. A lipidome-based visceral fat score may provide additional information over measured visceral fat for assessment of cardiometabolic health. Further studies are needed to test and validate the clinical utility of such lipidome-based scores.

Linkage and Association Studies between the Melanocortin Receptors 4 and 5 Genes and Obesity-Related Phenotypes in the Québec Family Study

No abstract is provided for this article.

[Psychiatric care without the patient's consent].

No abstract is provided for this article.

Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study

GREEN, J. S., P. R. STANFORTH, J. GAGNON, A. S. LEON, D. C. RAO, J. S. SKINNER, C. BOUCHARD, T. RANKINEN, and J. H. WILMORE. Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study. Med. Sci. Sports Exerc., Vol. 34, No. 1, 2002, pp. 74–82. Purpose To investigate the influences of menopause, hormone replacement, and endurance exercise training on cardiovascular hemodynamics and oxygen uptake parameters during exercise in women. Methods Subjects were 338 premenopausal women, 29 postmenopausal women taking hormone replacement, and 28 postmenopausal women not taking hormone replacement, all enrolled in the HERITAGE Family Study. Hemodynamic and oxygen uptake data were gathered on a cycle ergometer at 50 watts (W), 60% peak oxygen uptake, and at peak exercise, both before and after a 20-wk regimen of endurance exercise training on a cycle ergometer. Results Systolic blood pressure (SBP) during peak exercise was found to be an average of 14 mm Hg less in postmenopausal women receiving hormones than in those not receiving hormones. Furthermore, menopause was associated with a 26.2 mm Hg higher SBP at 50 W power output, which remained physiologically significant after adjustment for age. At 50 W, postmenopausal women not taking hormones showed a 13.8 mm Hg greater training-induced reduction in SBP than those taking hormones. Conclusion It was concluded that hormone replacement may be associated with a vasodilatory reserve at high exercise intensities and that endurance exercise training elicits favorable hemodynamic and oxygen uptake adaptations during exercise that are, in most instances, independent of menstrual status or hormone replacement.

High-range resolution radar for the identification of approaching targets: effects of parameters and measurements

With radar signals without compression, the resolution is fixed by the pulse lengths. For short targets, the scatterers are closely spaced and their echoes overlap making them indistinguishable. To overcome this, an algorithm based on the MUSIC algorithm was developed and simulations have shown the improvement on the radar's range resolution. In the present work, we have carried on with the simulations to estimate the effects of the most important parameters needed by the algorithm and we have made measurements to demonstrate the possible use of the method in the real world.

Adipose tissue distribution and plasma lipoprotein levels in obese women. Importance of intra-abdominal fat.

Prospective studies have shown that excess abdominal fat is associated with an increased risk of coronary heart disease and related death. We used computed axial tomography (CAT) to assess the association between deep and subcutaneous abdominal adipose tissue and plasma lipoprotein levels in a sample of 52 premenopausal obese women aged 35.7 +/- 5.5 years (mean +/- SD). Whereas the plasma lipoprotein concentration were not significantly correlated with fat mass, the data obtained by CAT indicated that the absolute amount of deep abdominal fat was negatively correlated with high density lipoprotein cholesterol (HDL-CHOL) levels (r = -0.35, p less than 0.01), as well as with HDL-CHOL/low density lipoprotein (LDL)-CHOL, HDL-apoprotein-(apo) A-I/LDL-apo B, and HDL2-CHOL/HDL3-CHOL ratios (-0.32 less than or equal to r less than or equal to -0.40, 0.05 greater than p less than 0.01). Adipose tissue deposition at the mid-thigh region determined by CAT did not show any significant relationship with plasma lipoprotein levels. When subgroups of women with comparable ages and adiposity but with high and low intra-abdominal fat accumulation were compared, women with a high accumulation of intra-abdominal fat displayed significantly lower HDL-CHOL (p less than 0.001), HDL2-CHOL (p less than 0.001), HDL3-CHOL (p less than 0.01), and HDL-apo A-I (p less than 0.05) levels, as well as reduced HDL-CHOL/LDL-CHOL (p less than 0.01), HDL-apo A-I/LDL-apo B (p less than 0.05), and HDL2-CHOL/HDL3-CHOL ratios (p less than 0.05) in comparison with obese women with low accumulations of intra-abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)