PPAR alpha L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

Background: Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components ( typically 50 - 80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome. Methods: We studied 610 young adult volunteers ( average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training. Results: We found the PPARa L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes ( LL = 116 +/- 11 mg/ dL, LV = 208 +/- 30 mg/ dL; p = 0.004). Men with the V allele showed lower HDL ( LL = 42 +/- 1 mg/ dL, LV = 34 +/- 2 mg/ dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume ( LL = - 1,707 +/- 21 mm(3), LV = 17,617 +/- 58 mm(3); p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARa L162V is on serum triglycerides, with downstream effects on adiposity and response to training. Conclusion: Our results on association of PPARa and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% ( p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males ( p = 0.0037)

Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Whey protein is a potential source of bioactive peptides. Based on findings from <it>in vitro </it>experiments indicating a novel whey derived peptide (NOP-47) increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans.</p> <p>Methods</p> <p>A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10) and women (n = 10) (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m²) participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47) or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD) and venous occlusion strain gauge plethysmography.</p> <p>Results</p> <p>Baseline peak FMD was not different for Placebo (7.7%) and NOP-47 (7.8%). Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively) whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; <it>P </it>< 0.0001 for time × trial interaction). Baseline reactive hyperemia forearm blood flow was not different for placebo (27.2 ± 7.2%/min) and NOP-47 (27.3 ± 7.6%/min). Hyperemia blood flow measured 120 min post-ingestion (27.2 ± 7.8%/min) was unaffected by placebo whereas NOP-47 significantly increased hyperemia compared to baseline (29.9 ± 7.8%/min; <it>P </it>= 0.008 for time × trial interaction). Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25%) compared to NOP-47 (-18%).</p> <p>Conclusion</p> <p>These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.</p

PPARα L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

<p>Abstract</p> <p>Background</p> <p>Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50–80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome.</p> <p>Methods</p> <p>We studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training.</p> <p>Results</p> <p>We found the PPARα L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 ± 11 mg/dL, LV = 208 ± 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 ± 1 mg/dL, LV = 34 ± 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 ± 21 mm³, LV = 17,617 ± 58 mm³; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARα L162V is on serum triglycerides, with downstream effects on adiposity and response to training.</p> <p>Conclusion</p> <p>Our results on association of PPARα and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).</p

INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men

Background A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G\u3eC, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population. Methods We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test. Results Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm3 vs. GC/CC: n = 181; 268521 ± 5003 mm3; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035). Conclusion Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation

A polymorphism near IGF1 is associated with body composition and muscle function in women from the Health, Aging, and Body Composition Study

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, −C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70–79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females

AKT1 polymorphisms are associated with risk for metabolic syndrome

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n = 175; age 40–65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations

Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat

<p>Abstract</p> <p>Background</p> <p>Genetic factors that predict responses to diet may ultimately be used to individualize dietary recommendations. We used physiogenomics to explore associations among polymorphisms in candidate genes and changes in relative body fat (Δ%BF) to low fat and low carbohydrate diets.</p> <p>Methods</p> <p>We assessed Δ%BF using dual energy X-ray absorptiometry (DXA) in 93 healthy adults who consumed a low carbohydrate diet (carbohydrate ~12% total energy) (LC diet) and in 70, a low fat diet (fat ~25% total energy) (LF diet). Fifty-three single nucleotide polymorphisms (SNPs) selected from 28 candidate genes involved in food intake, energy homeostasis, and adipocyte regulation were ranked according to probability of association with the change in %BF using multiple linear regression.</p> <p>Results</p> <p>Dieting reduced %BF by 3.0 ± 2.6% (absolute units) for LC and 1.9 ± 1.6% for LF (p < 0.01). SNPs in nine genes were significantly associated with Δ%BF, with four significant after correction for multiple statistical testing: rs322695 near the retinoic acid receptor beta (<it>RARB</it>) (p < 0.005), rs2838549 in the hepatic phosphofructokinase (<it>PFKL</it>), and rs3100722 in the histamine N-methyl transferase (<it>HNMT</it>) genes (both p < 0.041) due to LF; and the rs5950584 SNP in the angiotensin receptor Type II (<it>AGTR2</it>) gene due to LC (p < 0.021).</p> <p>Conclusion</p> <p>Fat loss under LC and LF diet regimes appears to have distinct mechanisms, with <it>PFKL </it>and <it>HNMT </it>and <it>RARB </it>involved in fat restriction; and <it>AGTR2 </it>involved in carbohydrate restriction. These discoveries could provide clues to important physiologic mechanisms underlying the Δ%BF to low carbohydrate and low fat diets.</p

Practical Assessment of Body Composition in Adult Obese Males

While several generalized regression equations exist for the prediction of body composition parameters in the normal adult population, the accuracy of these equations when applied to obese adults is uncertain. The present study examined the ability to predict body composition param- eters from girth measurements in obese men. One hundred twenty seven males with a body fat content of 30% or greater (as determined by hydro- static weighing at residual volume) were classified as obese (mean age = 46.8 ± 10.8 yrs, mean ht — 176.3 ± 6.5 cm, mean wt = 94.5 ± 13.2 kg, mean % body fat = 33.9 ± 3.2%, mean fat wt = 32.0 ±6.2 kg, mean lean body wt = 62.4 ± 8.4 kg). Girth measurements (cm) were taken at the following sites: chest, abdomen 1, abdomen 2, buttocks, and right thigh. Stepwise multiple regression analysis was applied to 84 randomly selected subjects with the following results (validation sample):Body Density = —0.00040 (mean abd) — 1.063, r = 0.50, Standard error of estimate = 0.0067 g/cc% Body Fat = 0.31457 (mean abd) — 0.10969 (wt) + 10.8336, r = 0.54, Standard error of estimate = 2.88% fatFat Wt = 0.22753 (wt) + 0.31341 (mean abd) - 22.608, r = 0.90, Standard error of estimate = 2.86 kgLean Body Wt = 0.77249 (wt) — 0.31353 (mean abd) + 22.620, r = 0.94, Standard error of estimate = 2.86 kgThese equations were cross validated on the remaining 43 subjects with the following cross validation results:Standard errorrof estimateBody Density0.380.006 g/cc% Body Fat0.442.50 % fatFat Wt0.902.67 kgLean Body Wt0.902.68 kgHence the use of girth measurements is a simple and practical method of estimating fat weight and lean weight in obese men

Association Of Age With Muscle Size And Strength Before And After Short-Term Resistance Training In Young Adults

Lowndes, J, Carpenter, RL, Zoeller, RF, Seip, RL, Moyna, NM, Price, TB, Clarkson, PM, Gordon, PM, Pescatello, LS, Visich, PS, Devaney, JM, Gordish-Dressman, H, Hoffman, EP, Thompson, PD, and Angelopoulos, TJ. Association of age with muscle size and strength before and after short-term resistance training in young adults. J Strength Cond Res 23(7): 19151920, 2009-The purpose of this study was to assess the association of age with muscle mass and strength in a group of young adults before and after 12 weeks of progressive resistance training. Eight hundred twenty-six young males and females (age 24.34 ± 5.69 yr, range 18-39 yr) completed a strictly supervised 12-week unilateral resistance training program of the nondominant arm. Isometric (maximal voluntary contraction [MVC]) and dynamic strength (1 repetition maximum [1RM]) of the elbow flexors and cross-sectional area (CSA) of the biceps-brachii using magnetic resonance imaging (MRI) scans were measured before and after training. Pearson correlation coefficients were calculated for size and strength variables and age. In addition, the cohort was divided into groups according to decade of life and differences assessed by analysis of variance. Age correlated significantly and positively with all pretraining measures of muscle size and strength (CSA: r =0.191, p \u3c 0.001; MVC: r =0.109, p = 0.002; 1RM: r = 0.109, p = 0.002). Age was not related to the training-induced changes in CSA or MVC but was negatively associated with the change in 1RM (r = -0.217, p \u3c 0.001). The study indicates that age does have a significant positive relationship with muscle size and strength in untrained young adults. Although age was negatively associated with improvements in 1RM, the effect of age was small relative to the improvements induced through resistance training, thus suggesting age does not limit response to training in any practical way during early adulthood. © 2009 National Strength and Conditioning Association