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Background: Despite adiponectin's presumed role in fatty acid oxidation and energy homeostasis, little is known about the effect of gene variants on substrate oxidation, energy expenditure, and adiposity-related phenotypes. Objective: We examined the effects of genetic variation in adiponectin (ADIPOQ) and adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) on resting metabolic rate, respiratory quotient (RQ), and adiposity-related phenotypes. Design: We studied the associations of ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms with resting metabolic rate, RQ, and body mass index, percentage body fat, sum of 6 skinfold thicknesses, waist circumference, and total, subcutaneous, and visceral fat in 759 participants in the Quebec Family Study. Results: The ADIPOQ 45T [right arrow] G single-nucleotide polymorphism (SNP) was significantly (P = 0.0002 to 0.04) associated with overall adiposity and abdominal adiposity; the rare homozygotes (G/G) had a leaner phenotype than did the carders of the common allele. One SNP each in the putative promoter of ADIPOR1 (ie, -3882T [right arrow] C) and ADIPOR2 (ie, IVS1 - 1352G [right arrow] A) was associated with RQ (P = 0.03 and 0.04, respectively), and the association was even stronger in nonobese persons (P = 0.02 and 0.003). Carriers of the common alleles (ADIPOR1 T and ADIPOR2 G alleles) had a lower RQ than did the rare homozygotes. A significant genotype-by-genotype interaction (P = 0.0002 to 0.02) was found between SNPs in the promoters of ADIPOQ (-3971A [right arrow] G) and ADIPOR1 (-3882T [right arrow] C). Subjects carrying the minor ADIPOQ allele (G allele) who were rare homozygotes (C/C) for the ADIPOR1 SNP had a higher RQ (P = 0.003) and greater overall (P < 0.03) and abdominal (P < 0.05) adiposity than did persons with other genotype combinations. Conclusions: Previous findings that the ADIPOQ 45T [right arrow] G variant contributes to overall fatness and abdominal obesity are confirmed. Moreover, variants in the promoter region of both ADIPOR genes contribute to substrate oxidation. KEY WORDS Adiponectin, adiponectin receptor, resting metabolic rate, respiratory quotient, obesity, abdominal obesity, adiposity

Background: Genes influencing resting metabolic rate (RMR) and respiratory quotient (RQ) represent candidate genes for obesity, type 2 diabetes, and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. Objective: We conducted a genome-wide scan for quantitative trait loci (QTL) contributing to the variability in RMR and RQ. Design: Regression-based and variance components-based genome-wide autosomal scans on RMR and RQ phenotypes, obtained from indirect calorimetry, were performed in 169 families ascertained via an obese proband or from the general population. Results: We found evidence for linkage to RMR on chromosomes 3q26.1 (lod = 2.74), 1q21.2 (2.44), and 22q12.3 (1.33). QTL influencing RQ were found on chromosomes 12q13 (1.65) and 14q22 (1.83) when the analyses were performed in all families. Considerable locus heterogeneity within this population was suggested because most of the families were unlinked to any one quantitative trait locus. Significant associations between traits and linked microsatellites were detected within the linked, informative subsets. Conclusions: We found several new QTL for energy metabolism, but the QTL on 1q may be a replication of the one reported in Pima Indians. All 3 RMR linkages overlapped regions previously linked to the metabolic syndrome or its components, and the significant association between RMR and the metabolic syndrome in the present cohort reinforces this relation. We conclude that considerable locus heterogeneity exists even within populations, which should be taken into account when considering candidate gene studies of energy metabolism phenotypes and other complex traits. KEY WORDS Resting metabolic rate, respiratory quotient, Quebec Family Study, linkage, locus heterogeneity, candidate genes

The 2005 update of the human gene map for physical performance and health related fitness phenotypes are presented. It is shown that little progress is made in the 12 months with respect to the genetic basis of human variation in performance and health-related fitness.

Background: The Agouti-related protein (AGRP), an appetite modulator, induces hyperphagia when administered intracerebroventricularly or when overexpressed in transgenic mice. Exogenous administration of AGRP in rodents predisposes to high fat and high sugar intakes. Objective: The objective was to examine the potential associations of 2 ethnic-specific polymorphisms in the AGRP gene (Ala67Thr in whites and - 38C>T in blacks) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. Design: We examined the effect of the 2 polymorphisms in the AGRP gene on self-reported macronutrient intakes in 478 white and 272 black participants in the HERITAGE Family Study. Results: Both AGRP polymorphisms showed a significant association with energy intake. In whites, a smaller proportion of total energy was derived from fat by the Ala67Thr heterozygotes ([bar.X] [+ or -] SEM: 29.4 [+ or -] 0.7%) than by the Ala67Ala homozygotes (31.5 [+ or -] 0.5%; P = 0.009), mainly because of a lower intake of saturated (P = 0.06) and monounsaturated (P = 0.01) fats by the Ala67Thr heterozygotes. The percentage of energy from carbohydrates was 2.6% greater in the Ala67Thr heterozygotes (55.1 [+ or -] 1.1%) than in the Ala67Ala homozygotes (52.5 [+ or -] 0.6%; P = 0.03). In blacks, protein intake was associated with the -38C>T promoter polymorphism. T/T homozygotes had a significantly lower protein intake than did the C-allele carriers (C/C: 16.8 [+ or -] 0.4%; C/T: 17.2 [+ or -] 0.2%; T/T: 15.4 [+ or -] 0.7%; P = 0.04). No significant differences in total energy and alcohol intakes existed between genotype groups in blacks or whites. Conclusions: The present study suggests that 2 ethnic-specific AGRP variants, previously shown to be associated with leanness in the HERITAGE Family Study, are also associated with macronutrient intake. KEY WORDS Agouti-related protein, AGRP, Ala67Thr, -38C>T, energy intake, macronutrient intake, food-frequency questionnaire, Quebec Family Study

We investigated the associations between the hepatic lipase gene (LIPC) -514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity ([S.sub.i]) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and [S.sub.i] were measured in the sedentary state and post-exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n = 662). The LIPC -514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post-exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HD[L.sub.3], and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post-exercise training. Baseline [S.sub.i] was not associated with the LIPC genotypes. However, training-induced improvements in [S.sub.i] both in blacks and whites were greater in CC homozygotes (+1.25 [+ or -] 0.2 and +0.22 [+ or -] 0.2 [micro]U x min-1 x [ml.sup.-1]) than in the TT genotype (+0.27 [+ or -] 0.3 and -0.97 [+ or -] 0.3 [micro]U x [min.sup.-1] x [ml.sup.-1]) (P = 0.008 and P = 0.002, respectively). The LIPC -514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better [S.sub.i] responses to regular exercise both in black and white individuals. The benefits from an exercise program on [S.sub.i] are likely to be substantial in the general population given the high frequency of the LIPC -514C allele, particularly in whites., Hepatic lipase hydrolyzes triglyceride and phospholipids from high-, intermediate-, and low-density lipoproteins, transforming them into smaller and denser particles, and promotes the cellular uptake of HDL cholesterol (1). The hepatic [...]

OBJECTIVE--To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (IVGTT). RESEARCH DESIGN AND METHODS--An IVGTT [...]

Background: Although regular physical activity is recommended for prevention of cardiovascular diseases, no data am available on its antiatherosderotic effects in the general population. Objective: To determine whether progressive aerobic exercise compared with usual activity slows progression of atherosclerosis in men. Design: A 6-year randomized, controlled trial. Setting: Eastern Finland. Participants: 140 middle-aged men randomly selected from the population registry. Intervention: Low-to moderate-intensity aerobic exercise. Measurements: Atherosclerosis was quantitated ultrasonographically as the mean intima-media thickness in the carotid artery at baseline and at years 2 through 6. Results: On the basis of intention-to-treat analyses, a 19.5% net increase (P < 0.001) in ventilatory aerobic threshold was evident in the exercise group after 6 years. High-sensitivity C-reactive protein levels were statistically nonsignificantly lower in the exercise group than in the control group (P > 0.2). The progression of intima-media thickness in the carotid artery did not differ between the study groups (P > 0.2). A subgroup analysis that excluded men taking statins showed that the 6-year progression of intima-media thickness, adjusted for smoking and annual measures of low-density lipoprotein cholesterol level, systolic blood pressure, and waist circumference, was 40% less in the exercise group (0.12 mm [95% Cl, -0.010 to 0.26 mm]) than in the control group (0.20 mm [Cl, 0.05 to 0.35 mm]). Limitations: Only middle-aged white men were included. The intervention included mainly aerobic exercises. Conclusions: Aerobic physical exercise did not attenuate progression of atherosclerosis, except in a subgroup of men not taking statins.

We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP Alga homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals., Type 2 diabetes is a multifactorial disease that results from a genetic predisposition and various behavioral and environmental risk factors (1). Regular physical activity has been associated with a reduced [...]

Background: A poor diet is a risk factor for chronic diseases such as obesity, cardiovascular disease, hypertension, and some cancers. Twin and family studies suggest that genetic factors potentially influence energy and nutrient intakes. Objective: We sought to identify genomic regions harboring genes affecting total energy, carbohydrate, protein, and fat intakes. Design: We performed a genomic scan in 347 white sibling pairs and 99 black sibling pairs. Dietary energy and nutrient intakes were assessed by using Willett's food-frequency questionnaire. Single-point and multipoint Haseman-Elston regression techniques were used to test for linkage. These subjects were part of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a multicenter project undertaken by 5 laboratories. Results: In the whites, the strongest evidence of linkage appeared for dietary energy and nutrient intakes on chromosomes 1p21.2 (P = 0.0002) and 20q13.13 (P = 0.00007), and that for fat intake appeared on chromosome 12q14.1 (P = 0.0013). The linkage evidence on chromosomes 1 and 20 related to total energy intake rather than to the intake of specific macronutrients. In the blacks, promising linkages for macronutrient intakes occurred on chromosomes 12q23-q24.21, 1q32.1, and 7q11.1. Several potential candidate genes are encoded in and around the linkage regions on chromosomes 1p21.2, 12q 14.1, and 20q13.13. Conclusions: These are the first reported human quantitative trait loci for dietary energy and macronutrient intakes. Further study may refine these quantitative trait loci to identify potential candidate genes for energy and specific macronutrient intakes that would be amenable to more detailed molecular studies. KEY WORDS Gene, quantitative trait locus, inheritance, food preference, linkage, energy intake

Several genome-wide linkage scans have been carried out to identify quantitative trait loci for type 2 diabetes and related metabolic phenotypes. However, no previous linkage scans have focused on the response to exercise training of relevant metabolic traits. We performed a genome-wide linkage scan for baseline fasting glucose, insulin, and C-peptide and their responses to a 20-week exercise training program in nondiabetic white and black men and women from the HERITAGE Family Study. In SIBPAL linkage analyses, the maximum number of sibpairs available was 344 and 93 for baseline phenotypes and 300 and 72 for exercise training response phenotypes in whites and blacks, respectively. A total of 509 markers with an average spacing of 6.0 Mb were used. The strongest linkage was found for the changes in fasting insulin in response to exercise training with a marker in the leptin gene on 7q31 (empirical multipoint P = 0.0004) in whites. In blacks, the strongest linkage was observed for baseline fasting glucose on 12q13-q14 (empirical multipoint P = 0.0006). These regions harbor several potential candidate genes. The present findings may be important in identifying individuals at increased risk of developing type 2 diabetes and who are most likely to benefit from a physically active lifestyle., Type 2 diabetes is a multifactorial heterogeneous disease characterized by variable degrees of insulin resistance and pancreatic β-cell dysfunction, which together lead to glucose intolerance (1). Chronic hyperglycemia, even below [...]

This article reviews current research on the relationship between human genetics and physical fitness levels. An analysis of cardiorespiratory endurance, muscle strength, gene mutation, and body composition measurements is presented.

Research shows that familial resemblance in physical activity and inactivity among the family members. Results indicate that the genetic factors and family environment determine only 16-25% of the physical activity or inactivity levels. Inactivity phenotype shows a slightly higher heritability level than that of physical activity phenotype.

Abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF) were measured using a computed tomography scan, both before (baseline) and after (post) a 20-week endurance exercise [...]

Research demonstrates that hormone replacement and vasodilatory property appear to show association at high intensity exercise. Further, favorable hemodynamic and oxygen consumption adaptations occur during endurance exercise training, which are independent of mensural status or hormone therapy.

This article investigates factors associated with individual differences in responses to controlled physical training. Findings indicate that sex, race, and age do not influence training responses but familial factors like shared environment and genetic similarities contribute to training response differences.

This article describes a human gene map used to help identify genetic differences related to physical performance and health. Traits such as endurance, muscular strength, metabolism, hemodynamic characteristics, and body composition are analyzed as genetic variables related to athletic ability and general health.

The high-affinity sulfonylurea receptor 1 (SUR1) plays an important role in regulating insulin secretion. In the Quebec Family Study, we genotyped 731 individuals (685 nondiabetic [ND] subjects) for the SUR1 [...]

Food intake, trace element status, and growth have been studied in schoolchildren and pubescent athletes. Club-level sports training in puberty does not seem to affect maturation or nutritional status or growth.

The most significant articles in exercise, fitness, and performance genomics and a brief overview of the first genome-wide association study of the genetic differences between exercisers and nonexercisers are reported. The findings recommended an urgent need to prioritize high-quality research designs and replication studies with large sample sizes.

An update of gene mapping of phenotypes that are related with physical performance and fitness in 2006-2007 is presented. Eighteen mitochondrial genes are found to have effect on performance and fitness phenotypes. The growing complexity of the gene map is also examined.

A subset of the 2004 update of the human gene map project focueses on physical performance and health-related fitness phenotypes. Information on peer-reviewed papers on this topic published in 2004 is presented. The genes and markers for sedentary people, people beginning sports training and very seasoned athletes are discusses. These genes and markers are positioned on the genetic map of all autosomes and the X chromosome.

A study is conducted to explore sex and race differences in the association between changes in fat mass (FM), abdominal visceral fat (AVF), and abdominal subcutaneous fat (ASF) on blood lipid changes consequent to aerobic exercise training. The multivariate associations among fat loss and changes in blood lipids consequent to aerobic exercise training are similar in African American and white men and women.

The 2003 update of the human gene map for physical performance and health-related fitness phenotypes is presented. It is based on pear-reviewed papers published by the end of 2003 and includes association studies with candidate genes, genome-wide scans with polymorphic markers, and single-gene defects causing exercise intolerance to variable degrees.

A study was done of the Heritage family in a standardized 20 wk training program to investigate whether genetic factors influenced the response to training. It revealed that heart rate (HR) at a given %VO(sub 2max) was not affected by training in a large heterogeneous group of men and women, blacks and white, who varied in fitness, age and response to training.

Research demonstrates that patients with metabolic syndrome risk factors benefit from the aerobic exercise training, which prevents them from developing chronic disease. The metabolic syndrome risk factors include elevated waist circumference, blood pressure, triglycerides, blood glucose, an low high-density cholesterol.

Research reveals familial aggregation of energy metabolism enzyme activities in the skeletal muscle both in the sedentary state and in response to regular exercise. Data show familial resemblance for Type I fiber area and familial aggregation for energy metabolism enzyme in the sedentary state, while with regard to training response familial aggregation is observed only for enzyme activities.

Research indicates linkage of physical inactivity to chromosome 2p22-p16 and suggestive linkages for other types of activities. Data point out that several chromosomal regions contain genes that either influence physically active or sedentary.

This article summarizes the number of genes and markers, identified until year 2002, that are known to exhibit an association or linkage on the X chromosome with a performance or fitness phenotype in sedentary or active subjects enganging in exercise.

Obesity and Type 2 diabetes mellitus (T2DM) have a complex genetic background and are strongly associated. Among genes possibly involved in both disorders, the IRS-1 gene is an interesting candidate [...]

The SUR1 plays an important role in the regulation of insulin secretion by the Beta cell. Recent studies have demonstrated an association between the T759T sequence variant and either Type [...]