Mark A Sarzynski

University of South Carolina | USC · Department of Exercise Science

Objective: Measures of HDL (high-density lipoprotein) function are associated with cardiovascular disease. However, the effects of regular exercise on these measures is largely unknown. Thus, we examined the effects of different doses of exercise on 3 measures of HDL function in 2 randomized clinical exercise trials. Approach and results: Radiol...

The purpose of the present study was to examine the effects of regular exercise on the abundance of targeted circulating microRNAs (miRNAs). The present analysis examined 20 previously sedentary adults from the HERITAGE Family Study who completed 20 weeks of endurance exercise training. The expression of 53 miRNAs related to cardiovascular disease...

Objectives We investigated whether high responsiveness or low responsiveness to exercise training aggregates in the same individuals across seven cardiometabolic traits. Methods A total of 564 adults (29.2% black, 53.7% female) from the HERITAGE family study completed a 20-week endurance training programme (at 55%–75% of participants’ maximal oxyg...

Maximal oxygen uptake (VO2max) is a direct measure of human cardiorespiratory fitness and is associated with health. However, the molecular determinants of interindividual differences in baseline (intrinsic) VO2max, and of increases of VO2max in response to exercise training (ΔVO2max), are largely unknown. Here, we measure ~5,000 plasma proteins us...

The aim of the HERITAGE Family Study was to investigate individual differences in response to a standardized endurance exercise program, the role of familial aggregation, and the genetics of response levels of cardiorespiratory fitness and cardiovascular disease and diabetes risk factors. Here we summarize the findings and their potential implicati...

Introduction: Angiopoietin like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of lipoprotein lipase and modifiable by regular exercise. However, the molecular biomarkers related to their exercise responses have not been fully elucidated. The purpose of this study was to examine the associations between plasma proteins and ANGPTL...

Introduction: Angiopoietin like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of lipoprotein lipase and modifiable by regular exercise. However, the molecular underpinning of these novel biomarkers has not been fully elucidated. The purpose of this study was to examine the associations between plasma metabolites and ANGPTL3/8 an...

High-throughput proteomics allow researchers to simultaneously explore the roles of thousands of biomarkers in the pathophysiology of diabetes. We conducted proteomic association studies of incident type 2 diabetes and physiologic responses to an intravenous glucose tolerance test (IVGTT) to identify novel protein contributors to glucose homeostasi...

Background: The US Dietary Guidelines (USDG) form the basis of nutrition guidelines, but the research informing the 3 USDG dietary patterns (Healthy US-Style [H-US], Mediterranean [Med], and vegetarian [Veg]) has been drawn largely from observational studies among White populations. Objectives: The Dietary Guidelines 3 Diets study was a 3-arm, 1...

Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. This metabolome-wide association study aimed to identify metabolomic markers for GWG. This longitudinal study included 39 Black and White pregnant women with a prepregnancy body mass index (BMI) of ≥ 25 kg/m2. Untargeted metabolomic profiling was performed using...

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensit...

Background: Whether higher cardiorespiratory fitness (CRF) confers protection against cardiovascular disease (CVD) in individuals with manifest hypercholesterolemia is poorly understood. Methods: Participants were 8920 men aged 20–82 years with hypercholesterolemia but no history of CVD and/or cancer and who received a preventive examination at the...

Introduction/purpose: Overweight or obese adults spend more time sedentary and less time performing physical activity (PA) and are at an increased risk for developing impaired glycemic health. Free-living environments may provide insight into glycemic health in addition to clinical assessments. The purpose of this study was to examine the relation...

High-throughput proteomic profiling using antibody or aptamer-based affinity reagents is used increasingly in human studies. However, direct analyses to address the relative strengths and weaknesses of these platforms are lacking. We assessed findings from the SomaScan1.3K ( N = 1301 reagents), the SomaScan5K platform ( N = 4979 reagents), and the...

This study aimed to assess if, during incremental exercise, considering individual characteristics can make the relationship between the percentages of heart rate (HRR) and oxygen uptake (VO2R) reserve either 1:1 or more accurate. Cycle ergometer data of the maximal incremental exercise tests performed by 450 healthy and sedentary participants (17-...

Integrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage genomic diversity for discovery. In addition, these analyses have principally involved known meta...

Background: Mass spectrometry (MS) profiling has identified over 250 proteins associated with HDL that are thought to underlie the diverse atheroprotective properties of HDL particles and thus may be important biomarkers of cardiovascular disease (CVD) risk. Likewise, recent studies have identified circulating plasma proteins as biomarkers of CVD r...

Introduction: Elevated plasma triglycerides (TG) are associated with risk of cardiovascular disease and are modifiable through lifestyle interventions such as regular exercise. However, TG responses to regular exercise are characterized by significant inter-individual differences. Hypothesis: We hypothesized that baseline levels of circulating prot...

Introduction: While high-density lipoprotein (HDL) cholesterol is a component of metabolic syndrome, an ASCVD risk factor, other markers of HDL metabolism better associate with ASCVD. However, it is unclear whether these markers better discriminate between metabolic health and obese groups. Hypothesis: We hypothesized that higher cholesterol efflux...

Background: The body of literature on discordance between lipoprotein cholesterol and particle concentrations focuses primarily on the relationship between lipoprotein discordance and clinical and subclinical indices of cardiovascular disease. Data are sparse regarding associations between either high (HDL) or low (LDL) density lipoprotein discorda...

Introduction: C-reactive protein (CRP) and GlycA are established biomarkers of inflammation. Regular exercise tends to decrease CRP and GlycA levels. However, the molecules underlying CRP and GlycA and their responses to exercise training are less known. Hypothesis: We hypothesized that distinct protein signatures exist for both baseline levels and...

Social agents associated with cheerleading environments are increasingly linked to body image dissatisfaction (BID) and eating disorders (ED). This study examined ED risk across team type, squad type, and position. An additional purpose determined BID in clothing type (daily clothing, midriff uniform, and full uniform), and meta-perceptions from th...

The purpose of this study was to examine individual and combined Female Athlete Triad components within collegiate cheerleaders, an at-risk group. Cheerleaders (n = 19; age: 20.3 ± 1.2 years) completed anthropometric measurements, health history questionnaires, resting metabolic rate, the eating disorder inventory-3 and symptom checklist, blood sam...

Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆)...

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence anal...

Glycemic variability is a more sensitive assessment of glycemic health as opposed to traditional clinical measurements. It considers all blood glucose concentrations over a given period to better account for glucose oscillations that occur and provides clinicians with insight into how individuals regulate and/or maintain their glycemic health. The...

Background The relationship between long‐term cardiovascular health (CVH) patterns and elevated CRP (C‐reactive protein) in late middle age has yet to be investigated. We aimed to assess this relationship. Methods and Results Individual CVH components were measured in 4405 Black and White men and women (aged 18–30 years at baseline) in the CARDIA...

The state of being overweight or obese leads to an increased risk of development of cardiometabolic disease. Increases in glycemic variability have been associated with greater induction of oxidative stress and declined vascular health, which may be exacerbated by higher weight status and improved through exercise. The purpose of this study was to...

Disruptions to muscle protein turnover and metabolic regulation contribute to muscle wasting during the progression of cancer cachexia. The initiation of cachexia is also associated with decreased physical activity. While chronic muscle AMPK activation occurs during cachexia progression in ApcMin/+ (MIN) mice, a preclinical cachexia model, the unde...

Introduction: Regular exercise beneficially increases plasma HDL-C levels at the group level. However, variation in individual HDL-C responses to exercise highlight a need for predictive biomarkers of exercise response. Hypothesis: We hypothesized that baseline abundance of circulating proteins is predictive of HDL-C response to exercise and that i...

Background: Body composition is known to differ across metabolic health and weight phenotypes. Regular exercise improves body composition, yet little is known about differences in exercise response across metabolic health and weight phenotypes. Methods: Normal weight (n=376) and overweight/obese (OWOB) adults (n=456) from the HERITAGE Family Study...

LIPOPROTEIN-INSULIN RESISTANCE (LPIR) SCORES DECREASED FOLLOWING AN OPTIFAST AND AEROBIC EXERCISE PROGRAM Emily Grammer1, Joshua McGee1, Taylor Brown1, Marie Clunan1, Anna Huff1, Briceida Osborne1, Laura Matarese1, Walter Pories1, Joseph Houmard1, Robert Carels1, Mark Sarzynski2, Damon Swift1 1East Carolina University, 2University of South Carolin...

Individual differences in physical performance in the sedentary state and in response to exercise training have been observed in rodent and human studies. The genomic variants underlying these genetic components are unknown. Nonetheless, without a rich genetic endowment, world-class athletic performance is out of reach.

Introduction: According to current guidelines, the intensity of health-enhancing aerobic exercise should be prescribed using a percentage of heart rate reserve (%HRR), which is considered to be more closely associated (showing a 1:1 relation) with the percentage of oxygen uptake reserve (%V[Combining Dot Above]O2R) rather than with the percentage...

Purpose: We designed the study to determine whether mitochondrial DNA (mtDNA) haplogroup, sequence, and heteroplasmy differed between individuals previously characterized as low (LR) or high responders (HR) as defined by their maximal oxygen uptake response to a standardized aerobic exercise training program. Methods: DNA was isolated from whole...

Importance Obesity is a major determinant of disease burden worldwide. Polygenic risk scores (PRSs) have been posited as key predictors of obesity. How a PRS can be translated to the clinical encounter (especially in the context of fitness, activity, and parental history of overweight) remains unclear. Objective To quantify the relative importance...

Proteins are effector molecules that mediate the functions of genes1,2 and modulate comorbidities3,4,5,6,7,8,9,10, behaviors and drug treatments¹¹. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized...

Importance Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual’s responsiveness to exercise interventions. Objective To investigate the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits befo...

Background/objectives: Overweight and obesity (OWOB) is a global epidemic. Adults and adolescents from low-income households are at higher risk to be OWOB. This study examined the relationship between income and OWOB prevalence in children and adolescents (518 years) in the United States (US) within and across race/ethnicities, and changes in this...

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability fol...

Intrinsic cardiorespiratory fitness (CRF) is defined as the level of CRF in the sedentary state. There are large individual differences in intrinsic CRF among sedentary adults. The physiology of variability in CRF has received much attention, but little is known about the genetic and molecular mechanisms that impact intrinsic CRF. These issues were...

Background Metabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-al...

Purpose of review: Low HDL-cholesterol (HDL-C) levels are a strong predictor of cardiovascular disease risk and can be improved with regular exercise. However, raising HDL-C levels pharmacologically has not shown convincing clinical benefits. Thus, research has recently focused on identifying therapies that improve HDL function, with exercise repr...

Background: Pairing a bout of high-intensity exercise with motor task practice can enhance motor learning beyond task practice alone, which is thought, in part, to be facilitated by an exercise-related increase in brain-derived neurotrophic factor (BDNF). The purpose of the current study was to examine the effect of different exercise intensities...

Background and aims: GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions. Met...

Background: Over 200 individual molecular lipid species have been found to reside on high-density lipoproteins (HDL). The effects of exercise on the HDL lipidome profile is unknown. Methods: We examined changes in the HDL lipidome after regular exercise in 20 individuals who completed a 20-week endurance exercise program as part of the HERITAGE Fam...

Introduction: In 2010, the American Heart Association (AHA) established “Life’s Simple 7” a composite of metrics aimed at defining cardiovascular health (CVH). Seven positive health factors (blood cholesterol, blood pressure, and fasting plasma glucose) and behaviors (diet quality, physical activity, smoking, and body mass index) are emphasized wit...

Introduction: Previous studies have shown that lipoprotein particle size and lipoprotein subclasses are associated with cardiovascular and type 2 diabetes risk, and have independent prognostic value above traditional lipid concentrations. The impact of exercise training and increasing non-exercise physical activity on lipoprotein subclasses and siz...

Objective: Many states in the southern region of the United States are recognized for higher rates of obesity, physical inactivity, and chronic disease. These states are therefore recognized for their disproportionate public health burden. The purpose of this study was to investigate state-level distributions of cardiorespiratory fitness, body mas...

Table S7. Differentially Expressed Proteins in the Eif6 Mitochondrial Proteome, Related to Figure 4

Document S1. Supplemental Experimental Procedures, Figures S1–S6, and Tables S1–S6

Table S8. Statistical Analysis of Eif6 Polysomal Microarray Data Compared to WT, Related to Figure 4

Regular endurance training improves muscle oxidative capacity and reduces the risk of age-related disorders. Understanding the molecular networks underlying this phenomenon is crucial. Here, by exploiting the power of computational modeling, we show that endurance training induces profound changes in gene regulatory networks linking signaling and s...

[This corrects the article DOI: 10.1371/journal.pgen.1006528.].

All SNPs that met significance for waist circumference adjusted for BMI in the European only analyses for at least one of the approaches tested: Interaction, adjusted for physical activity, or jointly accounting for the main and interaction effects. (XLSX)

All SNPs that met significance for BMI in the European only analyses for at least one of the approaches tested: Interaction, adjusted for physical activity, or jointly accounting for the main and interaction effects. (XLSX)

All SNPs that met significance for waist-to-hip ratio adjusted for BMI in the all ancestry analyses for at least one of the approaches tested: Interaction, adjusted for physical activity, or jointly accounting for the main and interaction effects. (XLSX)