β 2 - and β 3 -Adrenergic Receptor Polymorphisms Are Related to the Onset of Weight Gain and Blood Pressure Elevation Over 5 Years
Abstract
Background— The genes responsible for obesity are candidate genes for obesity-related diseases, such as hypertension. Functional polymorphisms in the β 2 - and β 3 -adrenergic receptors have been reported to be associated with hypertension and obesity. Methods and Results— To longitudinally clarify the relevance to alterations in β-adrenergic receptor polymorphisms related to weight gain, blood pressure (BP) elevation, and sympathetic nerve activity as measured by plasma norepinephrine level, we studied 160 young, nonobese, normotensive men. Changes in body weight, BP, plasma norepinephrine levels, and β 2 -adrenergic (Arg16Gly, Gln27Glu) and β 3 -adrenergic (Trp64Arg) receptor polymorphisms were measured periodically over a 5-year period. Weight gain and BP elevation were defined as ≥10% increases from entry levels over 5 years in body mass index or mean BP. The presence of the Gly16 allele of Arg16Gly was associated with a higher frequency of weight gain and BP elevation over the 5-year period. The subjects carrying the Glu27 allele of Gln27Glu and the Trp64 allele of Trp64Arg had a higher frequency of BP elevation. Significantly higher levels of plasma norepinephrine at entry and at year 5 were observed in the subjects with the Gly16 allele of Arg16Gly and the Glu27 allele of Gln27Glu compared with those without the Gly16 or the Glu27 alleles. Conclusions— These results demonstrate that the Gly16 allele is related to greater weight gain and BP elevation. Additionally, Glu27 and Trp64 alleles are linked to BP elevation. The subjects carrying the β 2 -polymorphisms linked to weight gain and BP elevation also have higher plasma norepinephrine levels that are present at entry before weight gain and BP elevation. These findings suggest that β 2 -adrenergic receptor polymorphisms in association with a heightened sympathetic nerve activity could predict the future onset of obesity and hypertension, as shown in the 5-year longitudinal study.
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The rate of lipolysis in adipose tissue during caloric restriction depends on sensitivity of β-adrenergic receptors to catecholamines like norepinephrine.
“The rate of lipolysis in adipose tissue during caloric restriction depends on the sensitivity of β-adrenergic receptors to catecholamines like norepinephrine.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [71]
Genetic differences in β2- and β3-adrenergic receptors affect receptor responsiveness, modulating the rate at which stored triglycerides are hydrolyzed into FFAs.
“Genetic differences in β2-adrenergic receptor and β3-adrenergic receptor affect receptor responsiveness, modulating the rate at which stored triglycerides are hydrolyzed into FFAs.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [71]
β2-adrenergic receptor Arg16Gly and Gln27Glu polymorphisms alter β2-adrenergic receptor sensitivity, impacting lipolytic response to catecholamines.
“The β2-adrenergic receptor Arg16Gly and Gln27Glu polymorphisms alter β2-adrenergic receptor sensitivity, impacting lipolytic response to catecholamines.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [71]
Individuals with heightened β-adrenergic sensitivity experience faster lipolysis, mobilizing fat stores more efficiently during restriction, whereas those with reduced sensitivity may struggle to achieve the same level of fat oxidation.
“Individuals with heightened β-adrenergic sensitivity experience faster lipolysis, mobilizing fat stores more efficiently during restriction, whereas those with reduced receptor sensitivity may struggle to achieve the same level of fat oxidation.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [71]
Individuals with high β-adrenergic sensitivity mobilize fat stores more effectively, supporting greater fat loss.
“Individuals with high β-adrenergic sensitivity mobilize fat stores more effectively, supporting greater fat loss [70,71].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [71]
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References 38 · Cited by 123
- Authors
- Masuo, K., Katsuya, T., Fu, Y., Rakugi, H., Ogihara, T., & Tuck, M. L.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Venue
- Circulation
- Published
- 2005-06-28
- Volume
- 111
- Issue
- 25
- Pages
- 3429-3434
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2035576585
- Cited by
- 123
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 8 · 2017: 3 · 2016: 1 · 2015: 5 · 2014: 12 · 2013: 3 · 2012: 7
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- beta2-adrenergic receptor, beta3-adrenergic receptor, genetic polymorphism, obesity, weight gain, hypertension, elevated blood pressure, plasma norepinephrine, sympathetic activity, Arg16Gly, Gln27Glu, candidate genes
- MeSH terms
- Adult, Blood Pressure, Body Weights and Measures, Genotype, Humans, Hypertension, Longitudinal Studies, Male, Middle Aged, Norepinephrine, Obesity, Polymorphism, Genetic, Sympathetic Nervous System, Weight Gain, Receptors, Adrenergic, beta-2, Receptors, Adrenergic, beta-3
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