Cited by 477Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesBlood Pressure and Hypertension Studies

Pathophysiological role of leptin in obesity-related hypertension

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Aizawa-Abe, Megumi, Ogawa, Yoshihiro, Masuzaki, Hiroaki, Ebihara, Ken, Satoh, Noriko, Iwai, Hidenori, Matsuoka, Naoki, Hayashi, Tatsuya +4 more·2000·Journal of Clinical Investigation

Abstract

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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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
Venue
Journal of Clinical Investigation
Published
2000-05-01
Volume
105
Issue
9
Pages
1243-1252
ISSN
0021-9738 (ISSN-L)
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
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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