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The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI<25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.

INTRODUCTION: Although exercise training can improve body composition, the molecular biomarkers and mechanisms related to these changes have not been fully elucidated. HYPOTHESIS: We hypothesized that distinct metabolite signatures exist for both baseline levels and exercise responsiveness of body composition traits, with substantial overlap across traits. METHODS: Measurements were taken before and after 20 weeks of endurance training in self-identified Black and White adults of the HERITAGE Family Study (n=652). 300 targeted plasma metabolites were measured using LC-MS. Underwater weighing, CT scans, and anthropometric measurements were used to derive the 11 body composition traits included in this study: BMI, body surface area, fat mass, fat free mass, %fat, waist circumference, waist-to-hip ratio, body weight, and abdominal visceral, subcutaneous, and total fat. Linear mixed models were used to test the association between plasma metabolites and each body composition trait at baseline and in response to training with full covariate adjustment. Significance was set to FDR&lt;0.05. Results: On average, subjects were [mean and (SD)] 35 (14) years old, 33% Black, 54% female, and had BMI of 26.2 (5.2) kg/m 2 . The number of metabolites significantly associated with body composition traits at baseline ranged from 57-141 ( Table 1 ). DMGV was among the top 3 associated metabolites at baseline for all 11 traits, while SM(d18:1/16:1) was associated with 8 of 11 baseline traits. Few if any significant associations were found between change in metabolites and change in body composition measures in response to exercise training (range: 0-10) ( Table 1 ). CONCLUSIONS: Although numerous metabolites were associated with body composition traits at baseline, few associations were observed with trait responses to training. These results suggest that intrinsic body composition and its response to exercise training may have differing underlying metabolic signatures.

The effects of exercise training and of its interaction with the genotype on components of energy expenditure and related hormones were examined in young male monozygotic twins. Energy intake was maintained at the pretraining level for a 93-day training period. The estimated net energy deficit induced by training was 244 MJ and was associated with a 5-kg body weight loss that was almost entirely explained by body fat loss. Resting metabolic rate (RMR) was significantly decreased by 8% after training despite the preservation of fat-free mass (FFM). Accordingly, plasma norepinephrine (NE) concentrations, NE appearance rate, and plasma levels of triiodothyronine (T3), free T3, and total thyroxine (T4) were lower after training. The energy cost of standardized exercise was also reduced after the training program. A modest to significant within—twin-pair resemblance was observed for absolute changes in the RMR, thermic effect of food, energy cost of exercise, NE clearance, and plasma concentrations of thyroid hormones. These results suggest that when exercise training is associated with a substantial negative energy balance, energy expenditure and levels of related hormones are decreased, and this effect is partly accounted for by heredity.

Six male monozygotic (MZ) twin pairs participated in the present study which was undertaken to assess the contribution of heredity to changes in plasma glucose and insulin in response to exercise-training. This group was submitted to a vigorous ergocycle exercise program inducing a surplus in energy expenditure of 1000 kcal/day over habitual energy expenditure during 22 consecutive days. An oral glucose tolerance test (OGTT, 75 g glucose) was performed before and about 16 hours after the experimental period. Fasting plasma glucose as well as its increase over basal level (Δ area) during OGTT were not modified by exercise-training (p > 0.05), although a marked reduction in insulin was observed, both in the fasting state and during the OGTT (p < 0.01). To assess the extent to which heredity influenced the response to the treatment, i.e. the genotype-training interaction, within and between MZ twin pairs means of squares were calculated. A significant intrapair resemblance in the response to exercise-training was observed for fasting insulin and Δ insulin area/Δ glucose area ratio during OGTT, but not for Δ insulin area. These results provide some indications about a possible role of the genotype on the sensitivity to reduce plasma insulin in response to exercise-training. However, this hypothesis needs to be substantiated by other experimental data with control over the genotype of subjects.

&lt;b&gt;&lt;i&gt;Background/Aim:&lt;/i&gt;&lt;/b&gt; Total fat intake has an important impact on the low-density lipoprotein (LDL) peak particle diameter (LDL-PPD) and may interact with nutrient-sensitive single nucleotide polymorphisms (SNPs). The objective was&lt;b&gt; &lt;/b&gt;to examine whether there is suggestive evidence of SNP × dietary fat intake interaction effects influencing the LDL-PPD in the Quebec Family Study (QFS) in order to generate hypotheses to be tested in larger studies. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; SNPs from a genome-wide association study (GWAS) using Illumina Human610-Quad BeadChip, total fat intake derived from a 3-day weighted food record, and SNP × total fat intake interaction effects were examined on LDL-PPD in 541 QFS subjects. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The GWAS analyses 29 identified independent SNP × total fat intake interaction effects on the LDL-PPD at p &lt; 10&lt;sup&gt;-5&lt;/sup&gt;, including SNPs in the following genes: &lt;i&gt;ABCG2, CPA3, FNBP1, KCNQ3, NBAS, NCALD, OPRL1, NKAIN2, SH3BGRL2, SOX5, &lt;/i&gt;and &lt;i&gt;SUSD4&lt;/i&gt;. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; This observational study suggests that multiple SNPs interact with dietary fat intake to influence variation in the LDL-PPD.

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.

Background: Clinical lipid measurements do not represent the full complexity of the effects of exercise on lipid metabolism. Lipidomics allows the assessment of hundreds of lipid species in response to exercise training. Methods: We examined changes in the plasma lipidome after regular exercise in 125 individuals who completed a 20-week endurance exercise program as part of the HERITAGE Family Study. Untargeted lipidomics profiling was performed on baseline and post-training plasma samples by CSH-ESI-QTOF mass spectrometry. Paired t-tests of log-transformed lipid values were used to determine the effects of exercise training. False discovery rate was controlled at 5% using the Benjamini–Hochberg procedure. Results: A total of 255 known lipid species were analyzed. The abundance of 173 lipid species across 11 lipid classes significantly changed with exercise training ( Table 1 ). Most lipid species significantly increased with exercise training, while only specific triacylglycerol species decreased (data not shown). The top overall hit was for PE 36:4 (p=1.4x10 -13 ), which increased 64% with exercise training. Replication of these results was explored in 25 HERITAGE subjects randomly selected for lipid profiling using the C8-positive method as part of an unrelated feasibility project. Data for 52 of the 173 top lipids were available in the 25 subjects. Of these, six lipids (PE 34:2, 36:4, 38:4, 38:6 and LPE 16:0, 38:4), including the top hits for PE and LPE ( Table 1 ), showed nominal (0.0002 &lt; p &lt; 0.04) training responses in the 25 subjects with the same directionality as observed in the larger sample. Discussion: Our study demonstrated extensive alterations in the plasma lipidome in response to regular endurance exercise. Future studies with larger sample sizes, diverse populations, and differing exercise protocols are needed to further examine how the plasma lipidome responds to exercise and potentially contributes to its cardioprotective effects.

Background: Previous studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease risk. However, the relationship between pCAD and the cardiometabolic profile in healthy adults, as well as the effects of regular exercise on pCAD are unknown. Methods: A total of 642 inactive but healthy adults (56% female, 36% Black, 35±13 yrs) completed 20 weeks of endurance exercise training. HDL-bound proteins were measured in APOA1-tagged serum using targeted LC-MS/MS (Quest Diagnostics). The pCAD index was calculated as a weighted sum of five HDL-associated apolipoproteins (APO A1, C1, C2, C3, C4) with scores from 0 to 100 (higher score=higher risk). Age-, sex-, and race-specific baseline pCAD quartiles were created. Results: The mean (SD) pCAD score at baseline was 29 (32). At baseline, increasing pCAD quartile was associated with a poorer cardiometabolic profile, including higher total and visceral fat, blood pressure, inflammation, and fasting glucose and lower insulin sensitivity and lipoprotein lipase activity ( Table ). In the total sample, pCAD significantly decreased with exercise training by 4.7 (25) pts or ~16%. Across pCAD quartiles, mean decreases in pCAD were 4.6 in quartile 3 and 21.3 in quartile 4, compared to mean increases of 3.6 in quartile 1 and 3.5 in quartile 2 (p&lt;0.05 for all within group changes). The exercise-induced decrease in pCAD was largely driven by increases in HDL-associated APOA1 and APOC1 levels and inversely correlated with changes in HDL-C (r= -0.17, p&lt;0.0001) and HDL size (r= -0.14, p=0.0006). Otherwise, changes in pCAD were not correlated with changes in other cardiometabolic traits. Conclusions: A higher pCAD index was associated with a poor cardiometabolic profile at baseline and improved with regular exercise in healthy adults with the worst profiles. These findings highlight the potential role of HDL apolipoproteins as a theranostic target for lifestyle interventions in these individuals.

An update of the human obesity gene map up to October 1996 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature, single‐gene mutation rodent models, quantitative trait loci uncovered 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. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all these loci reveals that only 4 of the 24 human chromosomes are not yet represented, i.e., 9, 18, 21, and Y. Several chromosome arms are characterized by the presence of several putative loci. The following arms include at least three such loci: 1p, 1q, 3p, 4q, 6p, 7q, 8p, 8q, 11p, 11q, 15q, 20q, and Xq. Studies with negative association and linkage results are also reviewed.

No abstract is provided for this article.