Mark A SarzynskiUniversity of South Carolina | USC · Department of Exercise Science
Mark A Sarzynski
Ph.D.
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279
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Introduction
Additional affiliations
July 2020 - present
August 2015 - June 2020
July 2014 - July 2015
Education
August 2004 - December 2008
Publications
Publications (279)
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...
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...
Regular exercise leads to widespread salutary effects, and there is increasing recognition that exercise-stimulated circulating proteins can impart health benefits. Despite this, limited data exist regarding the plasma proteomic changes that occur in response to regular exercise. Here, we perform large-scale plasma proteomic profiling in 654 health...
Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with dive...
BACKGROUND
ANGPTL3/4/8 (angiopoietin-like proteins 3, 4, and 8) are important regulators of LPL (lipoprotein lipase). ANGPTL8 forms complexes with ANGPTL3 and ANGPTL4. ANGPTL4/8 complex formation converts ANGPTL4 from a furin substrate to a plasmin substrate, and both cleavages generate similar C-terminal domain–containing (CD)—ANGPTL4 fragments. W...
Importance
Blood pressure response during acute exercise (exercise blood pressure [EBP]) is associated with the future risk of hypertension and cardiovascular disease (CVD). Biochemical characterization of EBP could inform disease biology and identify novel biomarkers of future hypertension.
Objective
To identify protein markers associated with EB...
Background: Prospective cohort studies have shown plasma cholesterol ester (CE) 18:2 is inversely associated with all-cause and cardiovascular mortality. However, less is known about the association of CE18:2 with cardiometabolic risk factors and whether it is responsive to regular exercise.
Methods: A total of 193 known plasma lipids, including 11...
Background: Excessive visceral fat is associated with metabolic alterations and is a causal risk factor for CVD. The plasma lipidome is altered in obesity and lipidome signatures of BMI and obesity have been identified. However, few studies have examined the plasma lipidome in relation to visceral fat.
Methods: Plasma lipids were measured using the...
Background: The lipoprotein insulin resistance (LP-IR) score has been shown to assess insulin resistance, predict future type 2 diabetes, and improve with regular exercise. The lipidomic profile is known to differ with insulin resistance and type 2 diabetes, but few studies have examined lipidome associations with LP-IR, particularly in response to...
Background
Standardized exercise protocols have been shown to improve overall cardiovascular fitness, but direct effects on left ventricular (LV) function, particularly diastolic function and relation to post-transcriptional molecular pathways (microRNAs (miRs)) are poorly understood. This project tested the central hypothesis that adaptive LV remo...
Angiopoietin-like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of LPL and novel therapeutic targets for dyslipidemia. However, the effects of regular exercise on ANGPTL3/8 and ANGPTL4/8 are unknown. We characterized ANGPTL3/8 and ANGPTL4/8 and their relationship with in vivo measurements of lipase activities and cardiometabolic...
Introduction: VO 2 max is the product of maximal cardiac output (Q) (maximal stroke volume (SVmax) x heart rate) and peak arterio-venous oxygen content difference (a-vO 2 diff). SVmax and peak a-vO 2 diff have important implications across the spectrum of human health and performance. However, the molecular mechanisms underlying SVmax and peak a-vO...
Background: Plasma proteins can be biomarkers of cardiovascular health status but also physiologic effectors that mediate health benefits. Cardiorespiratory fitness (CRF) is an integrative measure of cardiovascular and metabolic health and independent predictor of future cardiovascular disease (CVD) and mortality risk, however limited knowledge exi...
Introduction: Ischemic stroke is a complex heritable disease with a substantial proportion of risk attributable to polygenic factors. Little is known about how polygenic risk for stroke may manifest as intermediate phenotypes.
Hypothesis: Polygenic liability for ischemic stroke will be associated with cardiometabolic phenotypes even in young adults...
Submaximal exercise capacity is an indicator of cardiorespiratory fitness with clinical and public health implications. Submaximal exercise capacity and its response to exercise programs are characterized by heritability levels of about 40%. Using power output at a heart rate of 150 beats per minute (PWC150) as an indicator of submaximal exercise c...
Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma sam...
Background:
Regular exercise has many favorable effects on human health, which may be mediated in part by the release of circulating bioactive factors during each bout of exercise. Limited data exist regarding the kinetic responses of plasma proteins during and after acute exercise.
Methods:
Proteomic profiling of 4,163 proteins was performed us...
Aims:
Apolipoprotein C-II (ApoC-II) is thought to activate lipoprotein lipase (LPL) and is therefore a possible target for treating hypertriglyceridemia. Its relationship with cardiovascular risk has not been investigated in large-scale epidemiologic studies, particularly allowing for apolipoprotein C-III (ApoC-III), an LPL antagonist. Furthermore...
Background: Regular exercise has been shown to induce physiological adaptations such as improved left ventricle (LV) function, but LV diastolic function, particularly LV chamber stiffness (LV Kc) is rarely examined. In addition, the relation between changes in LV function, particularly LV Kc with regular exercise and post-transcriptional regulator...
Background: Chronic exercise protocols have demonstrated a beneficial effect on overall cardiovascular health, however, the direct effects on left ventricular (LV) function and the relation to changes in post-transcriptional regulatory checkpoints, that is the microRNAs (miRs), and what downstream processes may be affected, remains unexplored. Acco...
Background: Previous studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease risk. However, the relationship between pCAD and the cardiometabolic profile in healthy adults, as well as the effects of regular exercise on pCAD are unknown.
Methods: A total of 642 inactive but healthy adults (56% fe...
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 allows 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 homeostas...
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...
Introduction: The blood pressure (BP) response during acute exercise (acute exercise blood pressure (AEBP)) is related to future risk of hypertension (HTN) and cardiovascular disease (CVD). Biochemical characterization of AEBP could identify novel biomarkers of CVD risk and inform understanding of its biology.
Methods: We applied an aptamer-based p...
Introduction. C-reactive protein (CRP) and GlycA are established biomarkers of inflammation. Regular exercise tends to decrease CRP and GlycA levels. However, the spectrum of molecules associated with the anti-inflammatory effects of regular exercise are less well understood. Hypothesis. We hypothesized that distinct metabolite signatures exist for...
Introduction: Type 2 diabetes (T2D) is a cardiovascular disease risk equivalent and likely results from broad metabolic changes, which high throughput proteomics have helped to unravel. Prior studies are limited by proteomic coverage, cross sectional design, and lack of physiologic phenotyping.
Hypothesis: Complementary proteomic studies of inciden...
INTRODUCTION: Although exercise training can improve body composition, the molecular biomarkers and mechanisms related to these changes have not been fully elucidated.
HYPOTHESIS: We hypothesized that distinct metabolite signatures exist for both baseline levels and exercise responsiveness of body composition traits, with substantial overlap across...
Background: High-throughput metabolite profiling allows for the assessment of thousands of metabolites that may participate in exercise-related pathways. Here, we characterize plasma metabolite changes in healthy individuals undergoing endurance exercise training (ET) to identify biochemical features of VO 2 max and/or those responsive to ET.
Metho...
Introduction: Lipoproteins are among the strongest predictors of CVD and are altered through regular exercise. However, the molecular changes underlying the potential benefits of exercise on plasma lipoproteins are unclear.
Methods: Proteins (n=4979) were quantified from the plasma of 647 Black and White adults (56% women, mean age = 34.9 yrs) befo...
Introduction: Although exercise training is known to alter body composition, the molecular biomarkers and mechanisms related to these changes have not been fully elucidated. The purpose of this study was to examine the associations between plasma proteins and body composition traits before and after exercise training.
Methods: Measurements were tak...
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...
Introduction: Proteins are important regulators of cardiometabolic health that are increasingly recognized as being modulated by exercise.
Hypothesis: We measured approximately 5,000 plasma proteins before and after an endurance exercise training (ET) program to test the hypothesis that proteomic changes are related to adaptations in maximal oxygen...
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...
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...
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...