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PÉRUSSE, LOUIS, YVON C. CHAGNON, JOHN WEISNAGEL, AND CLAUDE BOUCHARD. The human obesity gene map: the 1998 update. Obes Res . 1999;7:111–129. An update of the human obesity gene map incorporating published results up to the end of October 1998 is presented. Evidence from the human obesity cases caused by single gene mutations; other Mendelian disorders exhibiting obesity as a clinical feature; quantitative trait loci uncovered in human genome‐wide scans and in crossbreeding experiments with mouse, rat, and pig models; association and case‐control studies with candidate genes; and linkage studies with genes and other markers is reviewed. The most noticeable changes from the 1997 update is the number of obesity cases due to single gene mutations that increased from three cases due to mutations in two genes to 25 cases due to 12 mutations in seven genes. A look at the obesity gene map depicted in Figure 1 reveals that putative loci affecting obesity‐related phenotypes are found on all but chromosome Y of the human chromosomes. Some chromosomes show at least three putative loci related to obesity on both arms (1, 2, 3, 6, 7, 8, 9, 11, 17, 19, 20, and X) and several on one chromosome arm only (4q, 5q, 10q, 12q, 13q, 15q, 16p, and 22q). The number of genes and other markers that have been associated or linked with human obesity phenotypes is increasing very rapidly and now approaches 27.

Relationships between cardiovascular risk factors and Heath-Carter anthropometric somatotype components were considered in 642 healthy adults free from overt disease: 68 males and 177 females, 30–39 years, and 233 males and 224 females, 40–49 years of age. Risk factors included systolic and diastolic blood pressures (SBP, DBP), fasting glycemia (GLYC), triglycerides (TG), plasma cholesterol (CHOL), the high density lipoprotein cholesterol fraction (HDL-C), and the HDL-C/CHOL ratio. Correlations between risk factors and each somatotype component were calculated after controlling for the effects of the other two somatotype components. Correlations were generally low and at best moderate, with significant correlations ranging from −0.23 to +0.23 in males and −0.20 to +0.30 in females. The relationships were stronger in the older group, 40–49 years, but the pattern of correlations was different in men and women. Endomorphy tended to be positively related to risk factors in older females, whereas ectomorphy tended to be negatively related to risk factors in older males. Comparison of somatotypes of individuals at the extremes of the distributions for each risk factor (upper and lower tertiles) were generally consistent with the direction of the correlations. For each cardiovascular risk, those with a poorer profile tended to be more endomorphic and mesomorphic and less ectomorphic than those with a better profile, who were more ectomorphic and less endomorphic and mesomorphic. The association was more apparent in males than in females and more so in those 40–49 years of age than in the younger age group. Although the correlations suggest that body type is weakly associated with common cardiovascular risk factors in healthy men and women, somatotype associations are more apparent at the extremes of the distributions of specific risk factors. Am. J. Hum. Biol. 9:11–19 © 1997 Wiley-Liss, Inc.

1340 High levels of plasma homocysteine are independently associated with an increased risk of coronary artery disease. Little information is available on the role of regular aerobic exercise on plasma homocysteine, and whether there are sex- or race-related differences in exercise training-induced changes in homocysteine. PURPOSE: To investigate the effects of relatively long-term regular exercise on plasma homocysteine concentrations in 730 black and white men and women, aged 17 to 65 years. METHODS: Concentrations of plasma total homocysteine were measured by the HPLC method. RESULTS: For the whole cohort, homocysteine levels remained unchanged between baseline (mean ± SD 8.8 ± 4.4 μmol/L) and post exercise training (8.9 ± 3.6 μmol/L). In Blacks, homocysteine levels did not change with training (men −0.5 ± 3.7μmol/L, women 0.0 ± 2.2μmol/L) but increased significantly (p<0.0001) in Whites (men +0.3 ± 1.7μmol/L, women +0.3 ± 1.6μmol/L). In men, there was a racial difference in changes in homocysteine. No sex-related differences were found in either racial group. Change in homocysteine levels were negatively correlated with baseline homocysteine (r = −0.60, p<0.0001). Homocysteine levels of the 'High (hyperhomocysteinaemia)' (≥15μmol/L) group decreased (p = 0.008) with regular ecxercise from 23.3 ± 11.9 μmol/L to 19.8 ± 7.6 μmol/L, while the homocysteine levels of the 'Normal' (<15μmol/L) group increased (p<0.0001) from 8.2 ± 2.2 μmol/L to 8.5 ± 2.4 μmol/L. CONCLUSIONS: In men, there were racial differences for the homocysteine changes in response to exercise training. Regular exercise had favorable effects on individuals with hyperhomocysteinaemia whereas homocysteine levels increased slightly in individuals within the normal range at baseline. Supported by the NHLBI through Grants HL45670, HL47323, HL47317, HL47327, and HL47321.

The reproducibility of responses to maximal cycle ergometer testing was determined using data from the HERITAGE Family study at four Clinical Centers in the United States and Canada.Reproducibility was determined from maximal exercise test data obtained a) on 2 d in a sample of 390 subjects (198 men and 192 women), b) across 4 d in an Intracenter Quality Control (ICQC) substudy with 55 subjects who were not part of the main study, and c) across 2 wk in a Traveling Crew Quality Control (TCQC) substudy with the same eight subjects who were tested at each of the four centers. Reproducibility was evaluated using technical errors, coefficients of variation (CV) for repeated measures, and intraclass correlation coefficients (ICC) for selected variables obtained on the main cohort, as well as on the ICQC and TCQC substudies.With the exception of systolic and diastolic blood pressures and respiratory exchange ratio, all the other variables (heart rate, ventilation, VO2, and VCO2) were highly reproducible, with CV below 10% and ICC over 0.86. These results were similar to those previously reported on the same subjects at a submaximal power output associated with 60% VO2max. Results were consistent for the main cohort, the ICQC sample, the TCQC sample, and across all four Clinical Centers.Day-to-day variations are small and reproducibility is high for maximal values of heart rate, ventilation, VO2 and VCO2 at each of the four Clinical Centers of the HERITAGE Family Study.

Regular exercise has many favorable effects on human health, which may be mediated in part by the release of circulating bioactive factors during each bout of exercise. Limited data exist regarding the kinetic responses of plasma proteins during and after acute exercise. Proteomic profiling of 4163 proteins was performed using a large-scale, affinity-based platform in 75 middle-aged adults who were referred for treadmill exercise stress testing. Plasma proteins were quantified at baseline, peak exercise, and 1-h postexercise, and those with significant changes at both exercise timepoints were further examined for their associations with cardiometabolic traits and change with aerobic exercise training in the Health, Risk Factors, Exercise Training and Genetics Family Study, a 20-week exercise intervention study. A total of 765 proteins changed (false discovery rate < 0.05) at peak exercise compared to baseline, and 128 proteins changed (false discovery rate < 0.05) at 1-h postexercise. The 56 proteins that changed at both timepoints included midkine, brain-derived neurotrophic factor, metalloproteinase inhibitor 4, and coiled-coil domain-containing protein 126 and were enriched for secreted proteins. The majority had concordant direction of change at both timepoints. Across all proteins assayed, gene set enrichment analysis showed increased abundance of coagulation-related proteins at 1-h postexercise. Forty-five proteins were associated with at least one measure of adiposity, lipids, glucose homeostasis, or cardiorespiratory fitness in Health, Risk Factors, Exercise Training and Genetics Family Study, and 20 proteins changed with aerobic exercise training. We identified hundreds of novel proteins that change during acute exercise, most of which resolved by 1 h into recovery. Proteins with sustained changes during exercise and recovery may be of particular interest as circulating biomarkers and pathways for further investigation in cardiometabolic diseases. These data will contribute to a biochemical roadmap of acute exercise that will be publicly available for the entire scientific community.

The aim of this study was to investigate the relationships between DNA restriction fragment length polymorphisms (RFLP) in the α 2 ‐ and β 2 ‐adrenoceptor genes and body fat distribution in humans. Skinfold thickness measurements and genetic analyses (Southern blot) were performed on 280 individuals (142 parents and 138 offsprings) from the Québec Family Study. Using the association study design in unrelated adults, women but not men carrying the 6.3‐kb allele of an α 2A ‐adrenoceptor/DraI RFLP had a significantly higher trunk to extremity skinfold ratio (= sum of subscapular + suprailiac + abdominal skinfolddsum of biceps + triceps + medial calf skinfolds) compared to women without the allele (1.44 ± 0.52 vs. 1.12 ± 0.33; p&lt;0.005 after adjustment for age, p&lt;0.002 after adjustment for age and body mass index or for age and subcutaneous fat). Using the sib‐pair linkage procedure, a significant inverse relationship was found between the proportion of alleles identical by descent shared by sibs at the α2A RFLP marker locus and the squared differences of thetrunk to extremity skinfold ratio (p = 0.02 after adjustment for age or for age and body mass index or for age and subcutaneous fat). For a β‐adrenoceptor/ BanI RFLP, no significant association or linkage was found between fat distribution indicators and the marker. These results suggest that α 2A ‐adrenoceptor gene variability detected with DraI is associated with a relative subcutaneous fat pattern favoring accumulation of truncal‐abdominal fat in women, and that the α 2A ‐adrenoceptogr ene, or a locus in close proximity, may be linked to body fat distribution in humans independently of the overall level of fatness.

No abstract is provided for this article.

In HEK293T cells there is a 3-fold repression of the luciferase reporter by miR-608 (Fig 1F), whereas a minor effect is observed at the level of AChE activity in U937 cells.What happens at the AChE protein levels in U937 cells?"We found this comment important and performed an immunoblot analysis for the AChE protein in U937 cells exposed to miR-608 compared to controls.A robust effect was observed at the level of the AChE protein, and, as we previously showed, this effect was considerably larger than that observed in the catalytic activity of the AChE enzyme, compatible with a large fraction of the AChE protein being catalytically inactive (as we previously reported in Shaked et al.Immunity 2009).Fig 1G in the manuscript had been revised accordingly, demonstrating a similarly robust suppression of the AChE protein by miR-132 and miR-608."The authors argue that the reduced interaction between miR-608 and AChE in the presence of the minor allele potentiates the repression of other miR-608 targets.However the Western-blot shown in Fig. 3B does not corroborate this conclusion/claim."To refine the presentation we replaced the presented blot with a more representative one.We hope that the outcome of greater difference between the control and the miR-608 treated cells for the major and minor alleles will be clearer in this revised figure ."Moreover, for the in vitro experiments the authors restrict their analysis to CDC42 (Fig 3B andC), while arguing for the same effect in other targets (e.g.IL-6).It is essential to check the effect for additional miR-608 targets.Along this line, it would be most interesting to use a genome-wide approach to look at the overall targets of miR-608."We found this comment of utmost importance for understanding the complexity aspect of miR-608 effects.To address this issue more globally, we used the miRwalk database (http://www.umm.uniheidelberg.de/apps/zmf/mirwalk/)to identify the top 30 predicted targets of miR-608, searched for those targets that are expressed in HEK293T cells (which incidentally do not express IL6) and designed RT-PCR primers for all of these predicted targets(Supplementary Table 2).We then performed a microfluidics dynamic array experiment (Fluidigm http://www.

A genome-wide linkage scan was performed to identify genomic regions that influence levels of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and DHEA fatty acid esters (DHEA-FA) at baseline and in response to 20 weeks of endurance exercise training in sedentary white and black participants in the HERITAGE Family Study. The baseline levels were log-transformed and adjusted for the effects of age and sex prior to genetic analysis. The training responses were adjusted for the effects of age, sex, and the baseline values. A total of 509 autosomal component polymorphic markers were used for the genome scan with an average spacing of 6.0 Mb. Multipoint variance components linkage analyses were performed in nuclear families containing 360 white and 106 black sibling pairs. We found 5 genomic regions with significant linkages for baseline DHEA-FA in whites, with log odd (LOD) scores over 3.6 (P [lt ] 2 [times ] 10[minus ]5). They include (1) D1S468 (LOD 4.56, 2.533 Mb, 1p36.22); (2) D2S177 (LOD 5.65, 52.663 Mb, 2p16.3); (3) D4S2397 (LOD 3.98, 32.246 Mb, 4p15.2); (4) the paraoxonase loci (LOD 3.93[sim ]3.99, 101.544[sim ]102.933 Mb, 7q21.3), and D7S821 (LOD 3.88, 104.497 Mb, 7q22.1); and (5) D12S372 (LOD 4.66, 2.129 Mb, 12q13.33). In addition, we obtained evidence of suggestive linkages (2.2 [lt ] LOD [lt ] 3.6; 2 [times ] 10[minus ]5 [lt ] P [lt ] 7 [times ] 10[minus ]4) on chromosomes 3p, 6q, and 8q for baseline DHEAS; on chromosomes 2q, 3p, 9q, 10p, 16q, and 17p for baseline DHEA-FA in whites; and on chromosomes 9q and 11p for baseline DHEA in blacks. This is the first genome-wide linkage scan searching for genomic regions influencing human DHEA levels. Several potential candidate genes are located in these genomic regions, which warrant further studies in HERITAGE and other cohorts.

A new compact cell for in situ synchrotron X-ray diffraction studies of adsorption or catalysis reactions has been designed to enable high performance whilst minimizing difficulties in use. It includes a system for simple insertion and alignment of capillary samples and an original miniaturized furnace providing excellent temperature homogeneity along the sample (temperature gradient less than 1 K over a 6 mm zone at 530 K). The efficiency of this setup is illustrated by in situ characterization of a zeolite (SrX) at four hydration levels.