Biomedical subjects

J Gagnon

Publications and source records attributed to J Gagnon.

At least 73 records · Page 4Linked to original sources

PubMed2000

Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study.

It has been suggested that genetic variation in the angiotensin-converting enzyme (ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian (n = 476) and black (n = 248) subjects. Phenotypes measured were oxygen uptake (VO(2)), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximal VO(2) (VO(2 max))] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60% VO(2 max)). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant (P values from 0.042 to 0. 0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14-38% greater increase with training in VO(2 max), VO(2) at 80% of VO(2 max), and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.

Adult↗

PubMed2000

Segregation analysis of apolipoproteins A-1 and B-100 measured before and after an exercise training program: the HERITAGE Family Study.

Complex segregation analyses of apolipoproteins (apo) A-1 and B-100 were performed in a sample of 520 individuals from 99 white families who participated in the HERITAGE Family Study. In these sedentary families, plasma apo A-1 and B-100 concentrations were measured before and after a 20-week endurance exercise training program. Baseline apo A-1 and B-100 were adjusted for the effects of age (age-adjusted baseline apo A-1 and B-100) and for the effects of age and BMI (age-BMI-adjusted baseline apo A-1 and B-100). The change in response to training was computed as a simple Delta (posttraining minus baseline) and was adjusted for age and the baseline (age-baseline-adjusted apo A-1 and B-100 responses to training). In the present study, a major gene could not be inferred for baseline apo A-1. Rather, we found a major effect along with a multifactorial effect accounting for 8% to 9% and 51% to 56% of the variance, respectively. In addition, no clear evidence supported a major-gene effect for its response to training, whereas the transmission of a major effect from parents to offspring was ambiguous, ie, genetic in nature or familial environmental in origin. The major effect accounted for 15% of the variance, with an additional 21% and 58% of the variance being accounted for by a multifactorial effect in parents and offspring, respectively. It is interesting to have obtained evidence of a putative recessive major locus for baseline apo B-100, which accounted for 50% to 56% of the variance, with an additional 25% to 29% of the variance due to a multifactorial effect. In contrast, no major effect for its response to training was identified, although a multifactorial effect was found that accounted for 27% of the variance. The novel findings arising from the present study are summarized as follows. Baseline apo A-1 and its response to training were influenced by a major effect and a multifactorial effect. Baseline apo B-100 was influenced by a putative major recessive gene with a multifactorial component, but its response to training was influenced solely by a multifactorial component in these sedentary families.

Adolescent↗

PubMed2000

Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in men and women: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) family study.

Abdominal obesity is associated with numerous metabolic alterations, such as hypertriglyceridemia and low levels of high density lipoprotein (HDL) cholesterol. However, compared with abdominally obese white individuals, abdominally obese black individuals have been characterized by higher plasma HDL cholesterol levels, suggesting that the impact of abdominal fat accumulation on the lipoprotein-lipid profile may differ among ethnic groups. Therefore, we have compared the associations between body fatness, visceral adipose tissue (AT) accumulation, and metabolic risk variables in a sample of 247 white men and 240 white women versus a sample of 93 black men and 143 black women. Although no difference in mean total body fatness was found between the 2 race groups, white men had higher levels of visceral AT than did black men (P<0.001). Despite the fact that black women had a greater body fat content than did white women, black women had levels of visceral AT that were similar to those of white women, suggesting a lower susceptibility to visceral obesity in black women. This lower accumulation of visceral AT in blacks was accompanied by significantly reduced apolipoprotein B concentrations and ratios of total cholesterol to HDL cholesterol as well as higher plasma HDL cholesterol levels (P<0.05) compared with those values in whites. Irrespective of sex, higher postheparin plasma hepatic lipase (HL) and lower lipoprotein lipase (LPL) activities were found in whites, resulting in an HL/LPL ratio that was twice as high in whites as in blacks (P<0.005). Although differences in lipoprotein-lipid levels were noted between whites and blacks, results from multiple regression analyses revealed that after control for morphometric and metabolic variables of the study (body fat mass, visceral AT, LPL, HL, and age), ethnicity had, per se, only a minor contribution to the variance in plasma lipoprotein levels. Thus, our results suggest that the higher plasma HDL cholesterol levels and the generally more cardioprotective plasma lipoprotein profile found in abdominally obese black versus white individuals are explained, at least to a certain extent, by a lower visceral AT deposition and a higher plasma LPL activity in black individuals.

Adipose Tissue↗

PubMed2000

NOS3 Glu298Asp genotype and blood pressure response to endurance training: the HERITAGE family study.

Endothelium-dependent vasodilation is a mechanism that may affect blood pressure response to endurance training. Because NO plays a central role in this process, the endothelial NO synthase gene is a good candidate for the regulation of exercise blood pressure. We investigated the associations between an endothelial NO synthase gene polymorphism (Glu298Asp) and endurance training-induced changes in resting and submaximal exercise blood pressure in 471 white subjects of the HERITAGE Family Study. Two submaximal exercise tests at 50 W were conducted both before and after a 20-week endurance training program. Steady-state exercise blood pressure was measured twice in each test with an automated unit. The Glu298Asp polymorphism was typed with a PCR-based method and digestion with BAN:II. Both systolic and diastolic blood pressure at 50 W decreased in response to the training program, whereas resting blood pressure remained unchanged. The decrease in diastolic blood pressure at 50 W was greater (P=0.0005, adjusted for age, gender, baseline body mass index, and baseline diastolic blood pressure at 50 W) in the Glu/Glu homozygotes (4.4 [SEM 0.4] mm Hg, n=187) than in the heterozygotes (3.1 [0.4] mm Hg, n=213) and the Asp/Asp homozygotes (1.3 [0.7] mm Hg, n=71). The genotype accounted for 2.3% of the variance in diastolic blood pressure at 50 W training response. Both the Glu298 homozygotes and the heterozygotes had a greater (P=0.013) training-induced reduction in rate-pressure product at 50 W than the Asp298 homozygotes. These data suggest that DNA sequence variation in the endothelial NO synthase gene locus is associated with the endurance training-induced decreases in submaximal exercise diastolic blood pressure and rate-pressure product in sedentary normotensive white subjects.

Adult↗

PubMed2000

Associations between the leptin receptor gene and adiposity in middle-aged Caucasian males from the HERITAGE family study.

Linkage and association studies between three exonic polymorphisms in the leptin receptor gene and body composition variables in the HERITAGE Family Study were undertaken. Polymorphisms K109R, Q223R, and K656N have been analyzed with body mass index (BMI), sum of height skinfolds (SF8), fat mass (FM), percent body fat (%FAT), fat free mass, and plasma leptin level. Single-point linkage analysis and covariance analysis across genotypes were performed, by race, on phenotypes adjusted for age and sex. Blacks (88 parents; 231 adult offspring) from 115 nuclear families (72-119 sibpairs) and Caucasians (192 parents; 330 adult offspring) from 99 nuclear families (319-364 sibpairs) were used for these analyses. In Caucasians, BMI and FM showed suggestive linkages with K109R (P = 0.02 and P = 0.05, respectively) and associations with Q223R (P = 0.005 and P = 0.03, respectively). In blacks, no statistically significant linkage or association was observed. In Caucasians, associations with Q223R were observed in parents, but not in offspring, for BMI, FM, and %FAT (0.04< or =P< or =0.0001). Males, not females, showed differences across genotypes for the same phenotypes plus SF8 and leptin (0.03< or = P< or =0.0002). Carriers of the R223 allele showed higher values than noncarriers for BMI (+4 U, P = 0.0001), SF8 (+30 mm, P = 0.01), FM (+7 kg, P = 0.0004), %FAT (+5%, P = 0.0002), and leptin (+4 ng/mL, P = 0.0006). These results indicate a significant effect of leptin receptor on adiposity in middle-aged Caucasian males.

Adipose Tissue↗

PubMed2000

Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE Family Study.

Obesity has been associated with alterations in plasma steroid hormone concentrations in men. Older men present an altered steroid hormone profile compared to younger individuals, and an increase in body fatness and changes in adipose tissue (AT) distribution are noted with advancing age. Thus, there is a need to examine the relative importance of increased body fatness and changes in AT distribution with advancing age to plasma steroid hormone and sex hormone-binding globulin levels in men. We, therefore, investigated the relationships among age, body fatness, AT distribution, and the plasma steroid hormone profile in a group of 217 Caucasian men (mean age +/- SD, 36.2 +/- 14.9 yr) who covered a wide age range (17-64 yr). Compared to young adult men, older men were characterized by increased adiposity (P < 0.0001) expressed either as body mass index or total body fat mass assessed by underwater weighing. Differences in AT distribution were also noted with a preferential accumulation of abdominal fat as indicated by a larger waist girth (P < 0.0001) and higher visceral AT accumulation (P < 0.0001), measured by computed tomography, in older subjects. Age was associated with decreases (P < 0.0001) in C19 adrenal steroid levels, namely reduced dehydroepiandrosterone (DHEA), DHEA fatty acid ester, DHEA sulfate, as well as androstenedione levels. Androgens, i.e. dihydrotestosterone and testosterone, were also affected by age, with lower levels of both steroids being found in older individuals (P < 0.0005). When statistical adjustment for body fatness and AT distribution was performed, differences in C19 adrenal steroids between the age groups remained significant, whereas differences in androgens and sex hormone-binding globulin concentrations were no longer significant. The present study suggests that age-related differences in plasma steroid hormone levels, especially androgens, are partly mediated by concomitant variation in adiposity in men.

Adipose Tissue↗

PubMed1999

The L392V mutation of presenilin 1 associated with autosomal dominant early-onset Alzheimer's disease alters the secondary structure of the hydrophilic loop.

Autosomal dominant early-onset Alzheimer's disease results mainly from mutations of the presenilin 1 (PSEN1) gene, which codes for an integral membrane protein of 467 amino acids. The hydrophilic loop (amino acids 263-407) of PSEN1, in which many pathogenic mutations have been localized, appears to be crucial for the protein function since it includes the binding domains to different PSEN1 partners. Using circular dichroism (CD) we analyzed the structural effects of the pathogenic L392V mutation and compared them with those of the E318G substitution. This study revealed that, the L392V mutation, in a phospholipidic medium which mimics the in vivo membrane environment, reduces the alpha helix content of the PSEN1 loop, whereas the E318G substitution, considered as a polymorphism, does not. These results suggest that the pathogenic effect of some PSEN1 mutations within the hydrophilic loop could be the alteration of the interaction to the different binding proteins through a disruption of the secondary structure.

Alzheimer Disease↗

PubMed1999

Characterization of a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase that displays glycopeptide N-acetylgalactosaminyltransferase activity.

We report the cloning, expression, and characterization of a novel member of the mammalian UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGaNTase) family that transfers GalNAc to a GalNAc-containing glycopeptide. Northern blot analysis revealed that the gene encoding this enzyme, termed ppGaNTase-T6, is expressed in a highly tissue-specific manner. Significant levels of transcript were found in rat and mouse sublingual gland, stomach, small intestine, and colon; trace amounts were seen in the ovary, cervix, and uterus. Recombinant constructs were expressed transiently in COS7 cells but demonstrated no transferase activity in vitro against a panel of unmodified peptides, including GTTPSPVPTTSTTSAP (MUC5AC). However, when incubated with the total glycosylated products obtained by action of ppGaNTase-T1 on MUC5AC (mainly GTT(GalNAc)PSPVPTTSTT(GalNAc)SAP), additional incorporation of GalNAc was achieved, resulting in new hydroxyamino acids being modified. The MUC5AC glycopeptide failed to serve as a substrate for ppGaNTase-T6 after modification of the GalNAc residues by periodate oxidation and sodium borohydride reduction, indicating a requirement for the presence of intact GalNAc. This suggests that O-glycosylation of multisite substrates may proceed in a specific hierarchical manner and underscores the potential complexity of the processes that regulate O-glycosylation.

Amino Acid Sequence↗

PubMed1999

Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child.

BACKGROUND: When thyroid deficiency occurs simultaneously in a pregnant woman and her fetus, the child's neuropsychological development is adversely affected. Whether developmental problems occur when only the mother has hypothyroidism during pregnancy is not known. METHODS: In 1996 and 1997, we measured thyrotropin in stored serum samples collected from 25,216 pregnant women between January 1987 and March 1990. We then located 47 women with serum thyrotropin concentrations at or above the 99.7th percentile of the values for all the pregnant women, 15 women with values between the 98th and 99.6th percentiles, inclusive, in combination with low thyroxine levels, and 124 matched women with normal values. Their seven-to-nine-year-old children, none of whom had hypothyroidism as newborns, underwent 15 tests relating to intelligence, attention, language, reading ability, school performance, and visual-motor performance. RESULTS: The children of the 62 women with high serum thyrotropin concentrations performed slightly less well on all 15 tests. Their full-scale IQ scores on the Wechsler Intelligence Scale for Children, third edition, averaged 4 points lower than those of the children of the 124 matched control women (P= 0.06); 15 percent had scores of 85 or less, as compared with 5 percent of the matched control children. Of the 62 women with thyroid deficiency, 48 were not treated for the condition during the pregnancy under study. The full-scale IQ scores of their children averaged 7 points lower than those of the 124 matched control children (P=0.005); 19 percent had scores of 85 or less. Eleven years after the pregnancy under study, 64 percent of the untreated women and 4 percent of the matched control women had confirmed hypothyroidism. CONCLUSIONS: Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore, screening for thyroid deficiency during pregnancy may be warranted.

Adult↗

PubMed1999

Molecular cloning and characterization of MT-ACT48, a novel mitochondrial acyl-CoA thioesterase.

While characterizing Eps15 partners, we identified a 48-kDa polypeptide (p48) which was precipitated by Eps15-derived glutathione S-transferase fusion proteins. A search in a murine expressed sequence tag data base with N-terminal microsequences of p48 led to the identification of two complete cDNA clones encoding two isoforms of a 439-amino acid protein sharing 95% nucleic and amino acid identity. Northern blot and immunoblotting studies showed that p48 was ubiquitously expressed. A significant homology (19% identity and 40% similarity) between p48 and rat brain cytosolic acyl-CoA thioesterase was observed in an 80-amino acid C-terminal domain, retrieved from proteins from human, nematode, and plants. The thioesterase function of p48 was further demonstrated against long chain acyl-CoAs in a spectrophotometric assay. Furthermore, data obtained from sequence analysis showed that p48 contained a mitochondrial targeting signal, cleaved in mature protein as assessed by microsequencing. The mitochondrial localization of both endogenous and transfected p48 was confirmed by confocal microscopy. These results indicate that p48, called MT-ACT48 (mitochondrial acyl-CoA thioesterase of 48 kDa), defines a novel family of mitochondrial long chain acyl-CoA thioesterases.

3T3 Cells↗

PubMed1999

Characterization of the conformational changes of acetohydroxy acid isomeroreductase induced by the binding of Mg2+ ions, NADPH, and a competitive inhibitor.

Acetohydroxy acid isomeroreductase (EC 1.1.1.86), the second enzyme of the parallel branched chain amino acid pathway, is a homodimer with an Mr of approximately 114000 which in the presence of Mg2+ ions catalyzes an unusual alkyl migration followed by an NADPH-dependent reduction. Prior binding of NADPH and Mg2+ to the enzyme was shown to be required for substrate or competitive inhibitor [N-hydroxy-N-isopropyloxamate (IpOHA)] binding [Dumas, R., et al. (1994) Biochem. J. 301, 813-820]. Moreover, crystallographic data for the enzyme-NADPH-Mg2+-IpOHA complex [Biou, V., et al. (1997) EMBO J. 16, 3405-3415] have shown that IpOHA was completely buried inside the active site. These observations raised the question of how the reaction intermediate analogue inhibitor can reach the active site and implied that conformational changes occurred during the binding process. With a view of characterizing these conformational changes, H-D exchange experiments combined with mass spectrometry were performed. Results demonstrated that Mg2+ ions and NADPH binding led to an initial conformational change at the interface of the two domains of each monomer. Binding of the two cofactors to isomeroreductase alters the structure of the active site to promote inhibitor (substrate) binding, in agreement with the ordered mechanism of the enzyme. Structural changes remote from the active site were also found. They were interpreted as long-range structural effects on the two domains and on the two monomers in the time course of the ligand binding process.

Alcohol Oxidoreductases↗

PubMed1999

Early and prolonged widespread increase in brain protein synthesis following a single electroconvulsive shock in free-moving rats.

The autoradiographic method with l-[35S] methionine ([35S]Met) was used to determine the effect of a single electroconvulsive shock (ECS) on local rates of protein synthesis in the adult rat brain in free-moving conditions. We have estimated the relative contribution of methionine derived from protein breakdown to the intracellular precursor amino acid pool (tRNA pool) for protein synthesis. In steady-state conditions, we showed a large contribution (around 60%) of Met recycling into the precursor pool (lambda=0.37+/-0.11), after a single ECS. In all the 36 brain regions examined, apparent rates of protein synthesis were greatly increased (21-50%) 3 h after a single ECS indicating a generalized effect in rat brain. This ECS-induced activation of the overall rate of brain protein synthesis persisted for at least 24 h after cessation of ECS. This is consistent with the hypothesis that electroconvulsive therapy is associated with long-term molecular changes in neuronal activity.

Analysis of Variance↗

PubMed1999

Body fat, resting and exercise blood pressure and the angiotensinogen M235T polymorphism: the heritage family study.

OBJECTIVE: The association of resting and exercise blood pressure (BP) and fat mass with the angiotensinogen (AGT) M235T polymorphism was investigated in 522 sedentary Caucasian subjects from 99 families. RESEARCH METHODS AND PROCEDURES: Resting BP was measured on two separate days, three times each day, and the mean of six valid measurements was used. Exercise BP was measured during a cycle ergometer test at a constant power output (50 W). Body composition was derived from under-water weighing and the AGT M235T polymorphism was typed with a polymerase chain reaction-based method. RESULTS: Neither resting nor exercise BP was associated with the AGT genotypes. In mothers, the homozygotes for the T allele showed 8.8 kg and 7.1 kg greater (p=0.017) age-adjusted body fat mass (FM) than the MM homozygotes and heterozygotes, respectively. Sixty-nine percent of all TT homozygotes were found in the highest FM tertile, whereas only 16% of the MM homozygotes fell in the same tertile (p = 0.008). Moreover, a significant interaction was seen between FM and T-allele carrier status in women with regard to resting diastolic BP (p = 0.002). Among women with a FM> or =24 kg, carriers of the T allele showed a 6.3 mmHg higher diastolic blood pressure (DBP) than non-carriers whereas no difference was found in women with a FM less than 24 kg. A similar trend toward an interaction term was evident with resting systolic blood pressure (p = 0.011) and exercise DBP (p = 0.012). Body fat was not associated with the AGT polymorphism in fathers or in offspring. DISCUSSION: These data suggest that the AGT M235T polymorphism is associated with body fatness in women, and that the relationship between DBP and AGT M235T polymorphism is dependent on FM in middle-aged sedentary normotensive women.

Adipose Tissue↗

PubMed1999

Plasma post-heparin lipase activities in the HERITAGE Family Study: the reproducibility, gender differences, and associations with lipoprotein levels. HEalth, RIsk factors, exercise Training and GEnetics.

OBJECTIVES: Examine the reproducibility of plasma lipid and lipoprotein measurements in the HERITAGE Family Study. DESIGN AND METHODS: In a sample of 379 subjects (191 men and 188 women), reproducibility was determined for lipids, lipoproteins (done on two occasions) and post-heparin lipase assays using an Intracenter Quality Control study by generating split samples from an additional 60 subjects (35 men and 25 women), which were assayed in a blind fashion by the lipid core laboratory. Reproducibility was estimated using intraclass correlation coefficients (ICC) for the selected variables. Analytical error (ANER) and coefficient of variation (CV) were also calculated. Day-to-day variation for 10 variables including plasma cholesterol and triglycerides (TG), HDL-cholesterol and its subfractions HDL2-cholesterol and HDL3-cholesterol, LDL-cholesterol and VLDL-cholesterol, as well as apoprotein (apo) A-I, apo B, and LDL-apo B were assessed. RESULTS: In the HERITAGE study, all lipid and lipoprotein variables had ICC above 0.79. Plasma VLDL-cholesterol (31 %) and TG (23%) levels, which are well known to be highly variable from one day to another, had CVs greater than 20%. Other variables had CVs lower than 10% except for HDL2-cholesterol which reached 16%. In the intracenter reliability sub-study, the measurement errors were found to be low except for HDL2-cholesterol. For the lipases, the reproducibility of repeated samples was very high, with ICC over 0.95. The within-assay CV corresponded to 2.1 and 5.3% for hepatic lipase (HL) and lipoprotein lipase (LPL), respectively, whereas the between-assay CV reached 8-12% for HL and about 15% for LPL. Due to the complexity of these two assays, the results are considered to be quite satisfactory. CONCLUSIONS: The reproducibility of plasma lipid and lipoprotein measurements, as well as of post-heparin lipase activities, is good in the multicenter HERITAGE Family Study. In addition, the well-documented gender difference in the plasma lipoprotein profile was confirmed in the present study, women having lower fasting triglyceride and LDL-cholesterol levels than men as well as reduced cholesterol/HDL-cholesterol and increased HDL2-cholesterol/ HDL3-cholesterol ratios compared to men. Results of the present study support the notion that the higher LPL and low HL activities found in women compared to men are important factors contributing to explain gender difference in the lipoprotein profile. However, additional factors not examined in the present study are involved beyond the contribution of post-heparin lipase to the sex dimorphism in plasma lipoprotein levels.

Female↗

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

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

Total body fat and abdominal visceral fat response to exercise training in the HERITAGE Family Study: evidence for major locus but no multifactorial effects.

The familial etiology of the response in total fat mass (FM) and abdominal visceral fat (AVF) to 20 weeks of exercise training was investigated in families participating in the HERITAGE Family Study. AVF (measured by computed tomographic scanning) and FM (measured by underwater weighing techniques) were assessed at baseline (in a sedentary state) and after 20 weeks of exercise training. The response AVF (AVFdelta) and response FM (FMdelta) were computed as the simple delta values (posttraining - baseline) and adjusted for the effects of sex, generation, and a polynomial in age using multiple regression analysis. To index the AVF response independently of the response in FM and the initial level of visceral fat, the AVFdelta was also adjusted for age and baseline AVF (AVFB) and FMdelta. Familial correlation analysis was used to investigate the multifactorial familial effects (polygenic and/or familial environmental), and segregation analysis was used to search for major gene effects. For the age-adjusted AVFdelta, a putative recessive locus accounting for 18% of the variance (q2 = 1%) was detected. Adjusting AVFdelta for AVFB and FMdelta slightly increased the percentage of variance accounted for (to 26%, q2 = 3%) but did not radically alter the pattern of the parameter estimates. For FMdelta, a putative dominant locus accounting for 31% of the variance (q2 = 49%) was noted. In conclusion, the results were consistent across methods in suggesting that there is little evidence of a multifactorial heritability for either AVFdelta or FMdelta. Rather, the familial etiology of the response to exercise training appears to be primarily due to putative major genes (a recessive locus for AVFdelta and a dominant locus for FMdelta). In addition, a pleiotropic/oligogenic system underlying these variables was inferred. That is, the putative loci for FMdelta and/or AVFB also may impact the AVFdelta, with an additional independent major locus effect on AVFdelta after the former influences have been removed.

Abdomen↗

PubMed1999

Familial aggregation of resting blood pressure and heart rate in a sedentary population: the HERITAGE Family Study. Health, Risk Factors, Exercise Training, and Genetics.

The familial aggregation of resting systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) was assessed in 98 white families, who participated in the HERITAGE Family Study, and were selected to be sedentary, and primarily nonobese and normotensive. In the present study, 522 family members were sedentary at baseline examination, and resting SBP, DBP, and HR measured during this examination were investigated. If physical activity level is a potent environmental factor, then we expected that the relative contribution of environmental factors to the familial aggregation of blood pressure (BP) would be somewhat reduced, because activity was controlled for in this study. Using a familial correlation model, maximal heritabilities were estimated to be 54%, 41%, and 32% for resting SBP, DBP, and HR, respectively, in these families; and they were 51%, 42%, and 34% for resting SBP, DBP, and HR, respectively, when the data were adjusted for body mass index. The estimates are somewhat higher for BP but similar for HR to those reported in previous family studies, suggesting that the distribution of the underlying etiologic factors in these sedentary families may be similar to those in the general population. There was substantial spouse resemblance in this study, which may be explained by a higher concordance for correlated lifestyle factors including diet, similar activity levels, or by assortative mating for relative weight or dietary preferences.

Adolescent↗