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. Author manuscript; available in PMC: 2013 Nov 15.
Published in final edited form as: Gene. 2012 Sep 5;510(1):66–70. doi: 10.1016/j.gene.2012.08.020

Leptin and Leptin Receptor Genetic Variants Associate with Habitual Physical Activity and the Arm Body Composition Response to Resistance Training

S Walsh 1, CJ Haddad 2, MA Kostek 2, TJ Angelopoulos 3, PM Clarkson 4, PM Gordon 5, NM Moyna 6, PS Visich 7, RF Zoeller 8, RL Seip 9, S Bilbie 9, PD Thompson 9, J Devaney 10, H Gordish-Dressman 10, EP Hoffman 10, Thomas B Price 11, LS Pescatello 2
PMCID: PMC3500611  NIHMSID: NIHMS405372  PMID: 22975643

Abstract

PURPOSE

We investigated the influence of Leptin (LEP) and leptin receptor (LEPR) SNPs on habitual physical activity (PA) and body composition response to a unilateral, upper body resistance training (RT) program.

METHODS

European-derived American volunteers (men=111, women=131, 23.4±5.4 yr, 24.4±4.6 kg·m−2) were genotyped for LEP 19 G>A (rs2167270), and LEPR 326 A>G (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183). They completed the Paffenbarger PA Questionnaire. Arm muscle and subcutaneous fat volumes were measured before and after 12wk of supervised RT with MRI. Multivariate and repeated measures ANCOVA tested differences among phenotypes by genotype and gender with age and body mass index as covariates.

RESULTS

Adults with the LEP 19 GG genotype reported more kcal/wk in vigorous intensity PA (1273.3±176.8, p=0.017) and sports/recreation (1922.8±226.0, p<0.04) than A allele carriers (718.0±147.2, 1328.6±188.2, respectively). Those with the LEP 19 GG genotype spent more hr/wk in light intensity PA (39.7±1.6) than A allele carriers (35.0±1.4, p=0.03). In response to RT, adults with the LEPR 668 G allele gained greater arm muscle volume (67687.05±3186.7 vs. 52321.87±5125.05 mm3, p=0.01) and subcutaneous fat volume (10599.89±3683.57 vs. −5224.73±5923.98 mm3, p=0.02) than adults with the LEPR 668 AA genotype, respectively.

CONCLUSION

LEP19 G>A and LEPR 668 A>G associated with habitual PA and the body composition response to RT. These LEP and LEPR SNPs are located in coding exons likely influencing LEP and LEPR function. Further investigation is needed to confirm our findings and establish mechanisms for LEP and LEPR genotype and PA and body composition associations we observed.

Keywords: exercise, genomics, polymorphism

1.1 Introduction

Leptin (LEP) is a hormone secreted mainly from adipose tissue that plays a role in regulating energy intake by its inhibitory effects on food intake and increases in energy expenditure by stimulating metabolic rate and physical activity (PA) to maintain energy balance (Lenard and Berthoud 2008). The biologic activities of LEP on target tissues are carried out through selective binding to its receptor (LEPR) (Paracchini et al 2005). LEPR exists in two isoforms: the long form (Ob-Rb) and short form receptors (Ob-Ra, c, d). It is a member of the class I cytokine receptor family that is expressed in the hypothalamus (Considine et al 1996) and peripheral tissues including skeletal muscle (Ceddia et al 2001). LEP acts as an afferent signal in a negative feedback loop by binding to LEPR regulating the size of adipose tissue (Sahu 2004).

Physical inactivity is a leading contributor to premature death and over 35 chronic diseases, including heart disease, diabetes mellitus, and obesity (Booth et al 2002). Despite overwhelming evidence of the many health benefits of physical activity, most people do not engage in the amount of PA necessary to achieve them (Lees and Booth 2004). Heritability studies show that genetic factors account for 20% to 70% of the variation in PA levels (Stubbe et al 2006), yet research examining the influence of genetic predispositions to be physically active, termed activity genetics, is scarce (Rankinen 2009; Rankinen et al 2010).

LEP activity is modulated by genetic variation. Hager et al. (Hager et al 1998) observed that a single A/G substitution at position 19, LEP 19 G>A (rs2167270), of the untranslated region of exon 1 effects LEP concentrations. Individuals homozygous for the LEP 19 G allele showed significantly lower LEP concentrations compared to those either heterozygous or homozygous for the A allele (Hager, Clement, Francke, Dina, Raison, Lahlou, Rich, Pelloux, Basdevant, Guy-Grand, North, and Froguel 1998). Several common polymorphisms of LEPR have also been identified to influence LEPR activity (Thompson et al 1997). LEPR 668 A>G (rs1137101) is located in exon 6, a putative LEP binding region. Chagnon et al. (Chagnon et al 1999) hypothesized that the single amino acid change of glutamine to arginine could alter the binding capacity of LEPR to LEP. LEPR genetic variants have also been associated with PA and 24 hr energy expenditure in humans (Stefan et al 2002). Stefan et al. (Stefan, Vozarova, Del, Ossowski, Thompson, Hanson, Ravussin, and Tataranni 2002) observed Pima Indians that were homozygous for the LEPR 668 A allele had lower 24 hr energy expenditure and lower PA levels assessed within in a respiratory chamber. Richert et al. (Richert et al 2007) found that boys 7 yr of age with the LEPR A668A genotype had lower self reported PA levels as determined by questionnaire than boys who were carriers of the G allele (Richert, Chevalley, Manen, Bonjour, Rizzoli, and Ferrari 2007).

Heritability estimates for body composition phenotypes range from 30% to 90% (Perusse et al 1996; Perusse et al 2005). LEP deficiency due to variation in the LEPR or LEP is associated with severe obesity in humans (Friedman and Halaas 1998; Sahu 2004). Investigators from the Quebec Family Study (Chagnon, Chung, Perusse, Chagnon, Leibel, and Bouchard 1999) observed three LEPR single nucleotide polymorphisms (SNPs) associated with body composition phenotypes, with the LEPR 668 A>G showing the strongest associations with fat free mass (Chagnon, Chung, Perusse, Chagnon, Leibel, and Bouchard 1999). Men who were carriers of the G allele with a body mass index < 27 kg/m2 had 4 kg less fat free mass than non-carriers of the G allele.

Therefore the aims of this present study were to examine whether two biologically relevant candidate genes, LEP and LEPR, are associated with habitual PA levels and the body composition response to a 12 wk unilateral, upper arm RT among a large sample of healthy, young normal weight adults. We hypothesized that LEP and LEPR genetic variants would associate with habitual PA and differentially impact the body composition response to a RT.

2.1 MATERIAL & METHODS

This sub-study was from a larger project entitled, Functional Single Nucleotide Polymorphisms Associated with Human Muscle Size and Strength (FAMuSS), conducted by the Exercise and Genetics Collaborative Research Group (Thompson et al 2004). Study protocol and informed consent were approved by the institutional review boards from the 10 sites involved with FAMuSS.

2.2 Subjects

Study participants were healthy European-derived American men and women 18 to 39 yr. Individuals did not qualify for participation if they self-reported a history of RT during the prior year, use of protein supplements during the prior 3 months, or alcohol consumption (>14 drinks/wk).

2.3 Physical activity measurements

A sub sample of FAMuSS subjects (n=560) completed the Paffenbarger Physical Activity Questionnaire (PPAQ) (Paffenbarger, Jr. et al 1995) during their initial visit. The PPAQ consisted of eight questions that quantified leisure-time PA levels. Questions 4 through 7 assessed leisure time exercise habits including sports and recreational activities. Question 8 asked subjects to divide a typical weekday and weekend day into hours spent in five intensity PA categories so that the total hours from each of the five categories totaled 24 hr. We considered all activities with a MET value >6 as vigorous intensity, MET value of 3–6 as moderate intensity, and MET value <3 as low intensity (Pate et al 1995). We then derived these PA phenotypes: Distance walked (mi/wk), PA index (kcal/wk), energy expended (EE) in vigorous and moderate intensity PA (kcal/wk), and sports and recreation (kcal/wk) as described previously (Ainsworth et al 1993; Paffenbarger, Jr., Wing, and Hyde 1995). Additional PA phenotypes included: Time (hr/wk) spent in vigorous, moderate, light intensity PA, and sitting (Paffenbarger, Jr. et al 1993).

2.4 Anthropometric measurements

Body weight and height were measured and recorded pre- and post-RT. Body weight was determined using a standard balance beam scale (Model 338 Eye-Level Physician Scale, Detectoscale, Webb City, MO) following the removal of shoes and heavy clothing. Body height was recorded in inches. Body mass index (kg m−2) was then calculated.

2.5 Resistance training program

All subjects participated in a 12 wk, 2 d/wk upper arm, unilateral RT program. All training was performed on the non-dominant arm. RT sessions were supervised and lasted approximately 45–60 min. Each RT session began with a warm-up consisting of two sets of 12 repetitions of the biceps preacher curl and seated overhead triceps extension. Five exercises were done in the following order: biceps preacher curl, seated overhead triceps extension, biceps concentration curl, triceps kickback, and standing biceps curl. Initial training weight was set at 65% one repetition maximum (1RM). There was a 2 min rest period between each set. RT was periodized to maximize muscle strength gains. Visits one to eight required three sets of 12 repetitions at 65–75% 1RM; visits nine to 18, three sets of eight repetitions at 75–82% 1RM; and visits 19 to 24, three sets of six repetitions at 83–90% 1RM.

2.6 Magnetic resonance imaging (MRI)

Cross-sectional area (CSA) of the biceps brachii was determined bilaterally using MRI with 1.5T systems and described in detail elsewhere (Kostek et al 2007; Walsh et al 2009). MRI was done pre-RT and within 48–96 hr of the final RT session. Prior to imaging, maximum arm circumference or point of measurement was ascertained and marked with a radiographic bead (Beekley Spots; Beekley Corp., Bristol, CT). The point of measurement was visually determined with a subject’s arm abducted 90° at the shoulder joint, palm supinated and open, and elbow flexed at 90°. The subject was then instructed to maximally flex the biceps muscles. The point of measurement was located, the skin marked, and the tip of a radiographic bead aligned and placed on the mark. The same investigator measured the point of measurement pre- and post-RT.

The MRI involved imaging a 24 cm length of the upper arm using 15 axial slices. Subjects were laid supine on the imaging bed, with the arm aligned to the isocenter of the magnet. The hand was placed in the anatomical position and affixed with tape to the scanner bed surface. Coronal and sagittal scout images were generated to locate the long axis of the humerus and to align the 8th axial slice with the point of measurement. With the point of measurement as the center point, 15 spoiled gradient images were taken [time to echo (TE) = 1.9 ms, time to repeat (TR) = 200 ms, flow artifact suppression, 30° flip angle]. Axial imaging began at the superior portion of the arm and proceeded distally toward the elbow joint. Each image slice was 16 mm thick with a 0 mm inter-slice gap, 256 x 192 matrix resolution, 22 cm x 22 cm filed of view, and number of experiments (NEX) = 6. MRI data from all investigational sites were submitted to the central imaging facility at Yale University via Magneto Optical Disk or CD-ROM for further analysis. Images were analyzed using a custom designed program created to function within Matlab (The Math Works, Inc., Natick, MA). The 8th slice was the location analyzed for biceps CSA pre- and post-RT. Subcutaneous fat and muscle volumetric measurements of the arm were calculated using the following equations, where C = 0.01 (conversion from pixels to squared centimeters) and trained = slice thickness (1.6 cm):

Subcutaneousfatvolume(mL)=∑(arm-lean)×C×trainedMusclevolume(mL)=∑(lean-bone)×C×trained

2.7 Genotyping methods

Genotyping was done to identify LEP and LEPR genotypes using TaqMan allele discrimination assays that employed the 5' nuclease activity of Taq polymerase to detect a fluorescent reporter signal generated during the PCR reaction. We genotyped the following SNPs: LEP 19 G>A (rs2167270), and LEPR 326 A>G (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183). Alleles were detected simultaneously using allele-specific oligonucleotides labeled with different fluorophores, and genotypes determined by the ratio of the two fluorophores used. Allele-specific PCR reactions for each single nucleotide polymorphism (SNP) included 10 ng genomic DNA, 900 nM forward and reverse PCR primers, 200 nM fluorescent allele discrimination probes and TaqMan® Universal PCR Master Mix, No AmpErase® UNG (Applied Biosystems, Foster City, CA, USA) in a final volume of 25 l. The PCR profile was 10 min at 95 °C (denaturation), and 44 cycles of 15 s at 92°C and 1 min at an annealing temperature of 60 °C. Reactions were set up using a MWG robot, and fluorescence ratios and allele calling done using an ABI 7900. For quality control, negative controls (water blanks) and duplicate samples covering 5% of the total number of samples analyzed (100% agreement) were included in the analysis.

2.8 Statistical analysis

Descriptive statistics were performed on all variables. All SNPs were in Hardy-Weinberg Equilibrium determined by χ2. The correlation coefficent method found that no SNPs were in linkage disequilibrium. Multivariate and repeated measures ANCOVA tested differences among PA and body composition phenotypes (i.e., subcutaneous fat volume and muscle volume) by LEP and LEPR genotype and gender, with age and body mass index as covariates. The phenotypes observed in the current study did not differ among LEP A19A and G19A genotype groups as well as among LEPR G668G and G668A genotype groups so these genotypes were combined and statistical analyses repeated on two genotype groups for each SNP using a dominant model, i.e., GG and GA/AA. All statistical analyses were performed with SPSS 15.0 for Windows with p<0.05 established as the level of statistical significance. A Bonferroni-correction was applied to account for multiple statistical testing. All data are reported as mean ± SEM. Data for SNPs where significant findings were observed are reported.

3.1 RESULTS

3.2 Subjects Characteristics

The study sample (n = 560) had a mean age of 23.4±5.4 yr and a BMI of 24.4±4.6 kg/m2. Age, weight, height, and BMI was greater in subjects homozygous for the LEPR 668 A allele versus those carrying the LEPR 668 G allele (p<0.05) (Table 1). No significant differences were observed for any physical characteristics by LEP 19 G>A, and LEPR 326 A>G (rs1137100) and 1968 G>C (rs8179183) genotypes (data not shown).

TABLE 1.

Mean Subject Characteristics by LEPR 668 A>G Genotype for Men and Women in the Resistance Training Cohort.

Variable AA (N=62) GG/GA (N=167)
Age (yr) 25.1 ± 0.7* 23.1 ± 0.4
Weight (kg) 74.5 ± 1.8* 69.4 ± 1.15
Height (cm) 172.4±0.4* 169.8±0.2
BMI (kg m−2) 25.1 ± 0.5* 23.1 ± 0.9
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Values are means ±SE. LEPR, Leptin Receptor; A, LEPR A668 allele; G, LEPR G668 allele; BMI, body mass index

*

P < 0.05, AA vs GG/GA

3.3 Physical Activity Phenotypes

Adults with the LEP 19 GG genotype reported more kcal/wk in vigorous intensity PA (p=0.017) and sports/recreation, (p=0.04) than A allele carriers (Table 2). Those with the LEP 19 GG genotype spent more hr/wk in light intensity PA than A allele carriers (p=0.03) (Table 2). No significant associations were observed among PA phenotypes and LEPR 326 A>G (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183) genotypes (data not shown).

Table 2.

Energy Expended and Time Spent Engaging in Physical Activity Intensity Categories Among Adults by LEP 19 G>A Genotype.

Variable GG (N= 103) AA/GA (N=139 )
Physical activity index (kcal/wk) 2961.9±246.8 2491.2±205.5
Vigorous intensity PA (kcal/wk) 1273.3±176.8 718.0±147.2*
Moderate intensity PA (kcal/wk) 629.6±107.2 530.4±89.3
Sports and recreation (kcal/wk) 1922.8±226.0 1328.6±188.2*
Light intensity PA (hr/wk) 39.7±1.6 35.0±1.4*
Sitting (hr/wk) 40.8±1.9 43.8±1.6
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Values are means ±SE. Covariates included age and body mass index. LEP, Leptin; A, LEP A19 allele; G, LEP G19 allele

*

GG vs AA/GA, p<0.05

3.4 Resistance Training

Biceps cross-sectional area

Carriers of the LEPR 668 G allele (n=166) gained greater absolute arm (p=0.007) and muscle CSA (p=0.007) (Table 3). In addition carriers of the LEPR 668 G allele gained more absolute subcutaneous fat CSA, while adults with the LEPR 668 AA genotype (n=62) lost subcutaneous fat CSA in the trained arm (p=0.002) (Table 3). No significant associations were observed among biceps CSA phenotypes and LEP 19 G>A, and LEPR 326 A>G (rs1137100), 3057 G>A (rs1805096), and 1968 G>C (rs8179183) genotypes (data not shown).

Table 3.

Cross-Sectional Area Changes in the Trained Arm in Response to RT by LEPR 668 A>G Genotype

Phenotype AA N=62 GG/GA N=166
Baseline whole arm cross sectional area (cm2) 6178.06 ± 90.6 6252.55±56.39
Post RT whole arm cross sectional area (cm2) 6744.40±97.0 6996.97±60.91
Absolute change (cm2) 566.33±55.1* 744.42±34.25
Relative change (%) 9.9±0.96* 12.2±0.59
Baseline whole muscle cross sectional area (cm2) 5308.85±168.68 5413.44±104.88
Post RT whole muscle cross sectional area (cm2) 5869.33±175.58 6138.85±109.17
Absolute change (cm2) 560.48±51.2* 725.39±31.84
Relative change (%) 12.17±1.05 14.17±0.65
Baseline subcutaneous fat cross sectional area (cm2) 2262.04±82.39 2291.36±51.23
Post RT subcutaneous fat cross sectional area (cm2) 2211.36±87.42 2380.40±54.36
Absolute change(cm2) −50.68±37.61* 89.03±23.39
Relative change (%) −1.95±1.86* 4.82±1.16
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Values are means ±SE. Covariates included BMI and age with LEPR genotype set as the fixed factor. LEPR, Leptin Receptor; A, LEPR A668 allele; G, LEPR G668 allele

*

P < 0.05, AA vs GG/GA

Biceps muscle and fat volume

Adults with the LEPR 668 G allele gained more arm muscle volume (p=0.01) and subcutaneous fat volume (p=0.02) than adults with the LEPR 668 AA genotype (Table 4). Adults with the LEPR 668 G also displayed relative gains in subcutaneous fat volume, while adults with the LEPR 668 AA genotype displayed decreases in subcutaneous fat volume (p=0.003) (Table 4). No significant associations were observed among biceps muscle and fat volume phenotypes and LEP 19 G>A, and LEPR 326 A>G (rs1137100), 3057 G>A (rs1805096), and 1968 G>C (rs8179183) genotoypes (data not shown).

Table 4.

Volume Changes in Trained Arm in Response to Resistance Training by LEPR 668 A>G Genotype

Phenotype AA N=62 GG/GA N=122
Baseline whole arm volume (mm3) 578037.66±8449.74 583481.81±5254.01
Post RT whole arm volume (mm3) 630588.66±8917.96 651499.52±5545.24
Absolute change (mm3) 52551.01±5070.75* 68017.71±3153.02
Relative Change (%) 9.78±0.95* 12.02±0.59
Baseline whole muscle volume (mm3) 494808.01±15341.97 504493.84±9557.60
Post RT whole muscle volume (mm3) 547205.86±15866.25 571038.04±9884.22
Absolute change (mm3) 52321.87±5125.05* 67687.05±3186.78
Relative Change (%) 12.09±1.05 13.94±0.65
Baseline subcutaneous fat volume (mm3) 211364.22±7549.02 211894.23±4702.82
Post RT subcutaneous fat volume (mm3) 206319.65±7937.28 219719.84±4944.70
Absolute change (mm3) −5224.73±5923.98* 10599.89±3683.57
Relative Change (%) −2.05±1.8* 4.61±1.1
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Values are means ±SE. Covariates included BMI and age with LEPR genotype set as the fixed factor. LEPR, Leptin Receptor; A, LEPR A668 allele; G, LEPR G668 allele

*

P < 0.05, AA vs GG/GA

4.1 DISCUSSION

The present study examined the influence of genetic variation in two biologically relevant candidate genes, LEP and LEPR, on habitual PA levels and the body composition response to a 12 wk unilateral, upper arm RT among a large sample of healthy, young normal weight adults. Important new findings were subjects homozygous for the LEP 19 G allele expended more energy in vigorous intensity PA (~555 kcal/wk) and sports and recreation (~594 kcal/wk), and spent more time in light intensity PA (~5 hr/wk) than carriers of the A allele. A difference in ~ 555 kcal/wk in vigorous intensity PA between LEP 19 G>A genotype groups may have significant health implications. Vigorous intensity PA is now an integral part of the updated physical activity recommendations for Americans (Haskell et al 2007; US Department of Health and Human Services 2008). The American College of Sports Medicine/American Heart Association update recommends participation in aerobic PA above minimum recommended amounts (at least 30 min of moderate intensity) because it provides additional health benefits, and results in greater gains in physical fitness and reductions in risk for premature chronic health conditions and mortality related to physical inactivity (Haskell, Lee, Pate, Powell, Blair, Franklin, Macera, Heath, Thompson, and Bauman 2007). Individuals homozygous for the LEP 19 G allele may be receiving additional health benefits as result of expending more energy in vigorous intensity PA due to their genetic predispositions than carriers of the A allele.

LEP has been shown to increase spontaneous PA (11) and LEP mediated increases in cocaine- and amphetamine-regulated transcript increases PA levels (Kristensen et al 1998). LEP administration also activates the sympathetic nervous system (Tang-Christensen et al 1999) and measurements of spontaneous PA in humans have been found to be related with sympathetic nervous system activity (Snitker et al 1997). Collectively, these findings suggest that differential circulating levels of LEP due to genetic variation may impact LEP mediated increases in cocaine- and amphetamine-regulated transcript and/or stimulation of sympathetic nervous system activity resulting in higher or lower PA levels that we observed in the current study. A limitation of the current study is that we do not have measures of circulating LEP concentrations. Thus, this hypothesis should be tested in future work attempting to replicate our findings.

Stefan et al. (Stefan, Vozarova, Del, Ossowski, Thompson, Hanson, Ravussin, and Tataranni 2002) and Richert et al (Richert, Chevalley, Manen, Bonjour, Rizzoli, and Ferrari 2007) observed genotype associations with PA levels in the LEPR 668 A>G while we did not. One explanation for these differences may be the result of different populations and measurement tools for the phenotypes of interest. Stefan et al. (Stefan, Vozarova, Del, Ossowski, Thompson, Hanson, Ravussin, and Tataranni 2002) examined a very genetically homogenous population in the Pima Indians and used a respiratory chamber to assess 24 hr energy expenditure and PA levels. Richert et al. (Richert, Chevalley, Manen, Bonjour, Rizzoli, and Ferrari 2007) studied boys 7 yr of age and determined PA levels by a self-report PA questionnaire. In contrast, our study population consisted of young healthy adults, and we used a self-report PA questionnaire. As result of these methodological differences, it is difficult to explain reasons for the different LEPR 668 A>G and PA findings among these studies.

The present study is one of few to examine the influence that genetic variation has on the body composition response to a RT program. Our new and noteworthy findings are adults with the LEPR 668 G allele not only gained greater muscle volume than adults with the LEPR 668 AA genotype but also greater subcutaneous fat volume, resulting in a 4.6% increase in subcutaneous fat. In comparison adults with the LEPR 668 AA genotype lost subcutaneous fat, displaying a 2% decrease in comparison to baseline values as a result of RT. Quinton et al. (Quinton et al 2001) found LEPR 668 A>G, which changes an amino acid and therefore potentially protein structure and function, associated with an impaired signaling capacity. LEPR 668 A>G has been associated with differences in body composition by others (Chagnon, Chung, Perusse, Chagnon, Leibel, and Bouchard 1999). Quinton et al. (19) concluded that variations in LEPR function associated with genotype are important factors in the regulation of adiposity (Quinton, Lee, Ross, Eastell, and Blakemore 2001).

We speculate that impaired signaling capacity of LEPR, as result of genotype, may explain the differences observed in the current study regarding the subcutaneous fat response to RT. Our research group has observed that a missense mutation in the SH2b1 gene (rs7498665) resulted in women with the rare allele gaining more subcutaneous fat than women with two copies of the common allele (Orkunoglu-Suer et al 2010). Similarly, another FAMuSS study from our research consortium reported PPARα L162V associated with the subcutaneous fat response to RT, with men carrying the rare allele gained considerably greater adiposity following unilateral resistance arm (Uthurralt et al 2007). Our previous reports (Orkunoglu-Suer et al 2011; Uthurralt, Gordish-Dressman, Bradbury, Tesi-Rocha, Devaney, Harmon, Reeves, Brandoli, Hansen, Seip, Thompson, Price, Angelopoulos, Clarkson, Moyna, Pescatello, Visich, Zoeller, Gordon, and Hoffman 2007) in combination with the present findings suggest that an interaction may exist between genetic profile and the body composition response to RT. Individuals who RT, with a certain genetic profile, may lead to poorer body composition response outcomes and limited localized exercise may trigger an increase in adiposity.

5.1 CONCLUSION

The present results adds LEP 19 G>A to a growing list of SNPs that have been identified as making contributions to the inter-individual variation in habitual PA levels and LEPR 668 A>G as influencing the body composition response to RT. Genetic factors influencing PA levels are now viewed as “the core” of the transdisciplinary model of exercise behavior. Therefore exercise genomics may provide an exciting new avenue that may add additional strategies in treating physical inactivity (Angela D.Bryan et al 2010). Elucidation of the genetic component of the body composition response to RT may be an important step toward development of novel and safe therapeutic strategies for reducing subcutaneous fat by developing individualized RT exercise prescriptions designed to maximize body composition changes. Potential mechanisms for these findings are unclear; therefore, further research is warranted to ascertain the physiologic pathways by which LEP 19 G>A differentially associates with habitual PA levels and LEPR 668 A>G with the body composition response to RT.

Highlights.

  • We examined genetic variation and its association with physical activity levels.

  • Leptin and Leptin Receptor SNP’s were the genetic variants examined.

  • LEP19 G>A associated with habitual physical activity.

  • LEPR 668 A>G associated with the body composition response to resistance training.

Acknowledgments

We thank the students and technicians at the participating institutions for their time and effort along with the subjects for their participation and commitment to the project.

Abbreviations

LEP

Leptin

PA

physical activity

LEPR

Leptin Receptor

SNPs

single nucleotide polymorphisms

FAMuSS

Functional Single Nucleotide Polymorphisms Associated with Human Muscle Size and Strength

RT

Resistance Training

PPAQ

Paffenbarger Physical Activity Questionnaire

EE

energy expended

1RM

one repetition maximum

MRI

Magnetic resonance imaging

CSA

Cross-sectional area

Footnotes

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