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Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice
Open accessAbstract
Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates active cortisol from inactive 11-keto forms, and aP2-HSD1 mice with relative transgenic overexpression of this enzyme in fat cells develop visceral obesity with insulin resistance and dyslipidemia. Here we report that aP2-HSD1 mice also have high arterial blood pressure (BP). The mice have increased sensitivity to dietary salt and increased plasma levels of angiotensinogen, angiotensin II, and aldosterone. This hypertension is abolished by selective angiotensin II receptor AT-1 antagonist at a low dose that does not affect BP in non-Tg littermates. These findings suggest that activation of the circulating renin-angiotensin system (RAS) develops in aP2-HSD1 mice. The long-term hypertension is further reflected by an appreciable hypertrophy and hyperplasia of the distal tubule epithelium of the nephron, resembling salt-sensitive or angiotensin II-mediated hypertension. Taken together, our findings suggest that overexpression of 11beta-HSD1 in fat is sufficient to cause salt-sensitive hypertension mediated by an activated RAS. The potential role of adipose 11beta-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder.
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“Expression of 11β-hydroxysteroid dehydrogenase (11β-HSD) in adipose tissue results in a mouse with abdominal obesity that develops hypertension (225).”
From Cardiac remodeling in obesity (2008) · cites this paper as [225]
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Cites
The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function
Goossens, G. H. (2017) · Obesity Facts · doi:10.1159/000471488 · Cited by 8,481
Kopelman, P. G. (2000) · Nature · doi:10.1038/35007508 · Cited by 4,795
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345
Self-citationSubcutaneous and visceral adipose tissue: their relation to the metabolic syndrome
Wajchenberg, B. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0415 · Cited by 2,961
The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis
Chrousos, G. P. (1992) · JAMA · doi:10.1001/jama.1992.03480090092034 · Cited by 2,689
Obesity and the regulation of energy balance
Spiegelman, B. M., & Flier, J. S. (2001) · Cell · doi:10.1016/s0092-8674(01)00240-9 · Cited by 2,398
Self-citationA transgenic model of visceral obesity and the metabolic syndrome
Masuzaki, H., Paterson, J., Shinyama, H., Morton, N. M., Mullins, J. J., Seckl, J. R., & Flier, J. S. (2001) · Science · doi:10.1126/science.1066285 · Cited by 1,766
Self-citationO'Brien, E. T., Sheridan, J., & O'MALLEY, K. (1988) · The Lancet · doi:10.1016/s0140-6736(88)92867-x · Cited by 1,032
Kotelevtsev, Y. V., Holmes, M. C., Burchell, A. N., Houston, P., Schmoll, D., Jamieson, P. M., Best, R., Brown, R., Edwards, C. R. W., Seckl, J. R., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14924 · Cited by 863
Self-citationDefinitions and characteristics of sodium sensitivity and blood pressure resistance.
Weinberger, M. H., Miller, J. Z., Luft, F. C., Grim, C. E., & Fineberg, N. S. (1986) · Hypertension · doi:10.1161/01.hyp.8.6_pt_2.ii127 · Cited by 775
Research works printed but not linked: 9
- Busetto, 2001, Nutr. Metab. Cardiovasc. Dis., 11, 195
- 10.1210/er.21.6.697 · DOI · Paper page
- 10.1210/jc.87.1.57 · DOI
- 10.1001/jama.267.9.1244 · DOI · Paper page
- 10.1210/jc.86.3.1418 · DOI
- 10.1210/en.141.2.560 · DOI
- Weinburger, 1986, Hypertension., 8(Suppl. II), II127
- Mills, 1993, Am. J. Physiol., 264, R73
- Contreras, 1989, Am. J. Physiol., 256, R1209
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Adipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522
Self-citationHolland, W. L., Brozinick, J. T., Wang, L.-P., Hawkins, E. D., Sargent, K. M., Liu, Y., Narra, K., Hoehn, K. L., Knotts, T. A., Siesky, A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.002 · Cited by 1,232
11β-Hydroxysteroid dehydrogenase type 1: a tissue specific regulator of glucocorticoid response
Tomlinson, J. W., Walker, E. A., Bujalska, I. J., Draper, N., Lavery, G. G., Cooper, M. S., Hewison, M., & Stewart, P. M. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0031 · Cited by 969
Seravalle, G., & Grassi, G. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.05.013 · Cited by 909
11β-hydroxysteroid dehydrogenases: Intracellular gate-keepers of tissue glucocorticoid action
Chapman, K., Holmes, M., & Seckl, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00020.2012 · Cited by 887
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Metadata
- Authors
- Masuzaki, H., Yamamoto, H., Kenyon, C. J., Elmquist, J. K., Morton, N. M., Paterson, J. M., Shinyama, H., Sharp, M. G. F., Fleming, S., Mullins, J. J., Seckl, J. R., & Flier, J. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of Edinburgh (GB)
- University of Dundee (GB)
- Corresponding author
- Flier, Jeffrey S.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2003-07-01
- Volume
- 112
- Issue
- 1
- Pages
- 83-90
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC162290
- OpenAlex
- W2127764698
- Cited by
- 434
- References
- 76
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 10 · 2018: 4 · 2017: 20 · 2016: 17 · 2015: 20 · 2014: 16 · 2013: 30 · 2012: 21
- FWCI
- 26.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Wellcome Trust
- National Institutes of Health (5r01dk059751-02)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK056116, DK56116, DK 59751)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- 11β-hydroxysteroid dehydrogenase type 1, adipose tissue, hypertension, salt-sensitive hypertension, renin-angiotensin system, angiotensin II, aldosterone, metabolic syndrome, obesity, transgenic mice
- MeSH terms
- Adipose Tissue, Animals, Glucocorticoids, Hydroxysteroid Dehydrogenases, Hypertension, Kidney, Male, Mice, Transgenic, Renin-Angiotensin System, Sodium Chloride, 11-beta-Hydroxysteroid Dehydrogenases, Mice
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