Alveolar air and oxidative metabolic demand during exercise in healthy adults: the role of single-nucleotide polymorphisms of the β2AR gene

Erik H. Van Iterson, Eric M. Snyder, Bruce David Johnson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The predominating β-adrenergic receptor subtype expressed on human alveolar tissue is the β2AR. The homozygous arginine (Arg16Arg) single-nucleotide polymorphism (SNP) at codon 16 of the β2AR gene has been associated with abnormal β2AR function accompanied by decreased resting alveolar-capillary membrane gas-transfer in certain healthy adults. Although not previously studied in the context of the β2AR gene, pulmonary gas-transfer is also influenced by alveolar volume (VA) and with it the availability of alveolar surface area, particularly during exercise. Small VA implies less alveolar surface area available for O2 transport. We tested the following hypothesis in healthy adults during exercise: compared with Gly16Gly and Arg16Gly β2AR genotypes, Arg16Arg will demonstrate reduced VA and ventilation (V̇A) relative to V̇E and oxidative metabolic demand. Age- BMI- and gender-matched groups of Arg16Arg (N = 16), Gly16Gly (N = 31), and Arg16Gly (N = 17) performed consecutive low (9-min, 40%-peak workload) and moderate (9-min, 75%-peak workload) intensity exercise. We derived VA and V̇A using “ideal” alveolar equations via arterialized gases combined with breath-by-breath ventilation and gas-exchange measurements; whereas steady-state V̇O2 was used in metabolic equations to derive exercise economy (EC = workload÷V̇O2). Variables at rest did not differ across β2AR genotype. Strongest β2AR genotype effects occurred during moderate exercise. Accordingly, while V̇E did not differ across genotype (P > 0.05), decreased in Arg16Arg versus Arg16Gly and Gly16Gly were V̇O2 (1110 ± 263, 1269 ± 221, 1300 ± 319 mL/(min·m2), respectively, both P < 0.05), V̇A (59 ± 21, 70 ± 16, 70 ± 21 L/min, respectively, both P < 0.05), and VA (1.43 ± 0.37, 1.95 ± 0.61, 1.93 ± 0.65 L, respectively, both P < 0.05). Also reduced was EC in Arg16Arg versus Arg16Gly (P < 0.05) and Gly16Gly (P > 0.05) (1.81 ± 0.23, 1.99 ± 0.30, and 1.94 ± 0.26 kcal/(L·m2), respectively). Compared with Gly16Gly and Arg16Gly genotypes, these data suggest the Arg16Arg β2AR genotype plays a role in the loss of oxidative metabolic efficiency coupled with an inadaptive VA and, hence, smaller alveolar surface area available for O2 transport during submaximal exercise in healthy adults.

Original languageEnglish (US)
Article numbere13476
JournalPhysiological Reports
Volume5
Issue number20
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Ventilation
Air
Exercise
Genotype
Genes
Gases
Workload
Codon
Adrenergic Receptors
Arginine
Research Design
Lung
Membranes

Keywords

  • Aerobic exercise
  • codon 16
  • exercise capacity
  • genetic polymorphism
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Alveolar air and oxidative metabolic demand during exercise in healthy adults : the role of single-nucleotide polymorphisms of the β2AR gene. / Van Iterson, Erik H.; Snyder, Eric M.; Johnson, Bruce David.

In: Physiological Reports, Vol. 5, No. 20, e13476, 01.11.2017.

Research output: Contribution to journalArticle

@article{654ed7e41093447fa8530b6b38b47854,
title = "Alveolar air and oxidative metabolic demand during exercise in healthy adults: the role of single-nucleotide polymorphisms of the β2AR gene",
abstract = "The predominating β-adrenergic receptor subtype expressed on human alveolar tissue is the β2AR. The homozygous arginine (Arg16Arg) single-nucleotide polymorphism (SNP) at codon 16 of the β2AR gene has been associated with abnormal β2AR function accompanied by decreased resting alveolar-capillary membrane gas-transfer in certain healthy adults. Although not previously studied in the context of the β2AR gene, pulmonary gas-transfer is also influenced by alveolar volume (VA) and with it the availability of alveolar surface area, particularly during exercise. Small VA implies less alveolar surface area available for O2 transport. We tested the following hypothesis in healthy adults during exercise: compared with Gly16Gly and Arg16Gly β2AR genotypes, Arg16Arg will demonstrate reduced VA and ventilation (V̇A) relative to V̇E and oxidative metabolic demand. Age- BMI- and gender-matched groups of Arg16Arg (N = 16), Gly16Gly (N = 31), and Arg16Gly (N = 17) performed consecutive low (9-min, 40{\%}-peak workload) and moderate (9-min, 75{\%}-peak workload) intensity exercise. We derived VA and V̇A using “ideal” alveolar equations via arterialized gases combined with breath-by-breath ventilation and gas-exchange measurements; whereas steady-state V̇O2 was used in metabolic equations to derive exercise economy (EC = workload÷V̇O2). Variables at rest did not differ across β2AR genotype. Strongest β2AR genotype effects occurred during moderate exercise. Accordingly, while V̇E did not differ across genotype (P > 0.05), decreased in Arg16Arg versus Arg16Gly and Gly16Gly were V̇O2 (1110 ± 263, 1269 ± 221, 1300 ± 319 mL/(min·m2), respectively, both P < 0.05), V̇A (59 ± 21, 70 ± 16, 70 ± 21 L/min, respectively, both P < 0.05), and VA (1.43 ± 0.37, 1.95 ± 0.61, 1.93 ± 0.65 L, respectively, both P < 0.05). Also reduced was EC in Arg16Arg versus Arg16Gly (P < 0.05) and Gly16Gly (P > 0.05) (1.81 ± 0.23, 1.99 ± 0.30, and 1.94 ± 0.26 kcal/(L·m2), respectively). Compared with Gly16Gly and Arg16Gly genotypes, these data suggest the Arg16Arg β2AR genotype plays a role in the loss of oxidative metabolic efficiency coupled with an inadaptive VA and, hence, smaller alveolar surface area available for O2 transport during submaximal exercise in healthy adults.",
keywords = "Aerobic exercise, codon 16, exercise capacity, genetic polymorphism, β-adrenergic receptor",
author = "{Van Iterson}, {Erik H.} and Snyder, {Eric M.} and Johnson, {Bruce David}",
year = "2017",
month = "11",
day = "1",
doi = "10.14814/phy2.13476",
language = "English (US)",
volume = "5",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "John Wiley and Sons Inc.",
number = "20",

}

TY - JOUR

T1 - Alveolar air and oxidative metabolic demand during exercise in healthy adults

T2 - the role of single-nucleotide polymorphisms of the β2AR gene

AU - Van Iterson, Erik H.

AU - Snyder, Eric M.

AU - Johnson, Bruce David

PY - 2017/11/1

Y1 - 2017/11/1

N2 - The predominating β-adrenergic receptor subtype expressed on human alveolar tissue is the β2AR. The homozygous arginine (Arg16Arg) single-nucleotide polymorphism (SNP) at codon 16 of the β2AR gene has been associated with abnormal β2AR function accompanied by decreased resting alveolar-capillary membrane gas-transfer in certain healthy adults. Although not previously studied in the context of the β2AR gene, pulmonary gas-transfer is also influenced by alveolar volume (VA) and with it the availability of alveolar surface area, particularly during exercise. Small VA implies less alveolar surface area available for O2 transport. We tested the following hypothesis in healthy adults during exercise: compared with Gly16Gly and Arg16Gly β2AR genotypes, Arg16Arg will demonstrate reduced VA and ventilation (V̇A) relative to V̇E and oxidative metabolic demand. Age- BMI- and gender-matched groups of Arg16Arg (N = 16), Gly16Gly (N = 31), and Arg16Gly (N = 17) performed consecutive low (9-min, 40%-peak workload) and moderate (9-min, 75%-peak workload) intensity exercise. We derived VA and V̇A using “ideal” alveolar equations via arterialized gases combined with breath-by-breath ventilation and gas-exchange measurements; whereas steady-state V̇O2 was used in metabolic equations to derive exercise economy (EC = workload÷V̇O2). Variables at rest did not differ across β2AR genotype. Strongest β2AR genotype effects occurred during moderate exercise. Accordingly, while V̇E did not differ across genotype (P > 0.05), decreased in Arg16Arg versus Arg16Gly and Gly16Gly were V̇O2 (1110 ± 263, 1269 ± 221, 1300 ± 319 mL/(min·m2), respectively, both P < 0.05), V̇A (59 ± 21, 70 ± 16, 70 ± 21 L/min, respectively, both P < 0.05), and VA (1.43 ± 0.37, 1.95 ± 0.61, 1.93 ± 0.65 L, respectively, both P < 0.05). Also reduced was EC in Arg16Arg versus Arg16Gly (P < 0.05) and Gly16Gly (P > 0.05) (1.81 ± 0.23, 1.99 ± 0.30, and 1.94 ± 0.26 kcal/(L·m2), respectively). Compared with Gly16Gly and Arg16Gly genotypes, these data suggest the Arg16Arg β2AR genotype plays a role in the loss of oxidative metabolic efficiency coupled with an inadaptive VA and, hence, smaller alveolar surface area available for O2 transport during submaximal exercise in healthy adults.

AB - The predominating β-adrenergic receptor subtype expressed on human alveolar tissue is the β2AR. The homozygous arginine (Arg16Arg) single-nucleotide polymorphism (SNP) at codon 16 of the β2AR gene has been associated with abnormal β2AR function accompanied by decreased resting alveolar-capillary membrane gas-transfer in certain healthy adults. Although not previously studied in the context of the β2AR gene, pulmonary gas-transfer is also influenced by alveolar volume (VA) and with it the availability of alveolar surface area, particularly during exercise. Small VA implies less alveolar surface area available for O2 transport. We tested the following hypothesis in healthy adults during exercise: compared with Gly16Gly and Arg16Gly β2AR genotypes, Arg16Arg will demonstrate reduced VA and ventilation (V̇A) relative to V̇E and oxidative metabolic demand. Age- BMI- and gender-matched groups of Arg16Arg (N = 16), Gly16Gly (N = 31), and Arg16Gly (N = 17) performed consecutive low (9-min, 40%-peak workload) and moderate (9-min, 75%-peak workload) intensity exercise. We derived VA and V̇A using “ideal” alveolar equations via arterialized gases combined with breath-by-breath ventilation and gas-exchange measurements; whereas steady-state V̇O2 was used in metabolic equations to derive exercise economy (EC = workload÷V̇O2). Variables at rest did not differ across β2AR genotype. Strongest β2AR genotype effects occurred during moderate exercise. Accordingly, while V̇E did not differ across genotype (P > 0.05), decreased in Arg16Arg versus Arg16Gly and Gly16Gly were V̇O2 (1110 ± 263, 1269 ± 221, 1300 ± 319 mL/(min·m2), respectively, both P < 0.05), V̇A (59 ± 21, 70 ± 16, 70 ± 21 L/min, respectively, both P < 0.05), and VA (1.43 ± 0.37, 1.95 ± 0.61, 1.93 ± 0.65 L, respectively, both P < 0.05). Also reduced was EC in Arg16Arg versus Arg16Gly (P < 0.05) and Gly16Gly (P > 0.05) (1.81 ± 0.23, 1.99 ± 0.30, and 1.94 ± 0.26 kcal/(L·m2), respectively). Compared with Gly16Gly and Arg16Gly genotypes, these data suggest the Arg16Arg β2AR genotype plays a role in the loss of oxidative metabolic efficiency coupled with an inadaptive VA and, hence, smaller alveolar surface area available for O2 transport during submaximal exercise in healthy adults.

KW - Aerobic exercise

KW - codon 16

KW - exercise capacity

KW - genetic polymorphism

KW - β-adrenergic receptor

UR - http://www.scopus.com/inward/record.url?scp=85032585713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85032585713&partnerID=8YFLogxK

U2 - 10.14814/phy2.13476

DO - 10.14814/phy2.13476

M3 - Article

C2 - 29061864

AN - SCOPUS:85032585713

VL - 5

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 20

M1 - e13476

ER -