Pathophysiological role of leptin in obesity-related hypertension
Open accessAbstract
To explore the pathophysiological role of leptin in obesity-related hypertension, we examined cardiovascular phenotypes of transgenic skinny mice whose elevated plasma leptin concentrations are comparable to those seen in obese subjects. We also studied genetically obese KKA(y) mice with hyperleptinemia, in which hypothalamic melanocortin system is antagonized by ectopic expression of the agouti protein. Systolic blood pressure (BP) and urinary catecholamine excretion are elevated in transgenic skinny mice relative to nontransgenic littermates. The BP elevation in transgenic skinny mice is abolished by alpha(1)-adrenergic, beta-adrenergic, or ganglionic blockers at doses that do not affect BP in nontransgenic littermates. Central administration of an alpha-melanocyte-stimulating hormone antagonist causes a marked increase in cumulative food intake but no significant changes in BP. The obese KKA(y) mice develop BP elevation with increased urinary catecholamine excretion relative to control KK mice. After a 2-week caloric restriction, BP elevation is reversed in nontransgenic littermates with the A(y) allele, in parallel with a reduction in plasma leptin concentrations, but is sustained in transgenic mice overexpressing leptin with the A(y) allele, which remain hyperleptinemic. This study demonstrates BP elevation in transgenic skinny mice and obese KKA(y) mice that are both hyperleptinemic, thereby suggesting the pathophysiological role of leptin in some forms of obesity-related hypertension.
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Leptin infusion in ob/ob mice raised their blood pressure despite causing significant weight loss.
“Leptin infusion in ob/ob mice raised their BP despite causing significant weight loss131.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [131]
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Obesity and the kidney: mechanistic links and therapeutic advances
Yau, K., Kuah, R., Cherney, D. Z. I., & Lam, T. K. T. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-00951-7 · Cited by 91 · see citing works
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Obesity-related hypertension: Is there a role for selective leptin resistance?
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Differential effects of insulin on sympathetic nerve activity in agouti obese mice
Morgan, D. A., & Rahmouni, K. (2010) · Journal of Hypertension · doi:10.1097/hjh.0b013e32833c2289 · Cited by 46 · see citing works
Control of metabolic and cardiovascular function by the leptin–brain melanocortin pathway
do Carmo, J. M., da Silva, A. A., Dubinion, J., Sessums, P. O., Ebaady, S. H., Wang, Z., & Hall, J. E. (2013) · IUBMB Life · doi:10.1002/iub.1187 · Cited by 36 · see citing works
Loss of Leptin Actions in Obesity: Two Concepts with Cardiovascular Implications
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Cardiovascular and Sympathetic Effects of Disrupting Tyrosine 985 of the Leptin Receptor
Harlan, S. M., Morgan, D. A., Dellsperger, D. J., Myers, M. G., Mark, A. L., & Rahmouni, K. (2011) · Hypertension · doi:10.1161/hypertensionaha.110.166538 · Cited by 24 · see citing works
- Authors
- Aizawa-Abe, M., Ogawa, Y., Masuzaki, H., Ebihara, K., Satoh, N., Iwai, H., Matsuoka, N., Hayashi, T., Hosoda, K., Inoue, G., Yoshimasa, Y., & Nakao, K.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Ogawa, Yoshihiro
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2000-05-01
- Volume
- 105
- Issue
- 9
- Pages
- 1243-1252
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC315441
- OpenAlex
- W2122722123
- Cited by
- 477
- References
- 60
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 12 · 2016: 14 · 2015: 10 · 2014: 20 · 2013: 15 · 2012: 18
- FWCI
- 12.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Naito Foundation
- Uehara Memorial Foundation
- Mitsubishi Foundation
- Japan Society for the Promotion of Science (98L00801, 96100204)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- leptin, obesity-related hypertension, hyperleptinemia, agouti protein, melanocortin system, catecholamine excretion, blood pressure regulation, adrenergic blockade, caloric restriction, dietary intake
- MeSH terms
- Adrenergic alpha-Antagonists, Adrenergic beta-Antagonists, alpha-MSH, Animals, Blood Pressure, Body Weight, Energy Intake, Eating, Ganglionic Blockers, Heart, Heart Rate, Hypertension, Kidney, Male, Mice, Transgenic, Models, Biological, Melanocyte-Stimulating Hormones, Obesity, Organ Size, Sympathetic Nervous System, Systole, Urine, Hexamethonium, Leptin, Mice
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