Obesity-Related Hypertension and the Role of Insulin and Leptin in High-Fat–Fed Rabbits
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Feeding a high-fat diet (HFD) to rabbits results in increased blood pressure and renal sympathetic nerve activity (RSNA) and marked increases in plasma leptin and insulin. We determined the contribution of insulin and leptin signaling in the central nervous system to the increased blood pressure and RSNA during a HFD using specific antagonists. New Zealand White rabbits were implanted with an intracerebroventricular (ICV) catheter and RSNA electrode and placed on a normal or 13.5% HFD for 1 or 3 weeks. Blood pressure, heart rate, and RSNA were recorded before and for 90 minutes after ICV administration of a leptin antagonist (100 µg), insulin antagonist (0.5 U), or vehicle (50 µL) on separate days. Rabbits had higher blood pressure (+8%, +17%) and RSNA (+55%, +71%), at 1 and 3 weeks, respectively, of HFD compared with controls (n=7–11). ICV leptin antagonist reduced blood pressure by 9% and RSNA by 17% ( P <0.001) after 3 weeks of HFD but had no effect at week 1. ICV administration of the insulin antagonist reduced blood pressure by ≈5% at both times ( P <0.05) but there was no effect on RSNA. Leptin and insulin antagonist doses were confirmed to effectively block the pressor responses to ICV leptin and insulin, respectively. The elevation of blood pressure and RSNA induced by a HFD is predominantly mediated by central actions of leptin. Central actions of insulin contribute a smaller proportion of the hypertension but independently of RSNA.
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Leptin receptor antagonism decreased blood pressure and sympathetic nerve activity in obese rabbits.
“The observation that LepR antagonism decreased BP and SNA in obese rabbits supports the importance of leptin in obesity hypertension129.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [129]
Administration of a leptin receptor antagonist reduced BP and renal SNS activity in obese rabbits fed a high fat diet.
“administration of a leptin receptor antagonist reduced BP and renal SNS activity in obese rabbits fed a high fat diet92.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [92]
Administration of a leptin receptor antagonist reduced blood pressure and renal sympathetic nervous system activity in obese rabbits.
“Administration of a leptin receptor antagonist reduced BP and renal SNS activity in obese rabbits supporting a role for endogenous leptin in mediating obesity-induced increases in BP [48].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [48]
Mutations of the POMC gene or the MC4R are estimated to account for as much as 5-6% of early onset obesity in humans.
“Mutations of the POMC gene or the MC4R are estimated to account for as much as 5–6% of early onset obesity in humans (48, 64).”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [48]
Leptin contributes to sympathetic overactivity and hypertension in a number of animal models of monogenic and diet-induced obesity.
“A large body of evidence has demonstrated that leptin contributes to sympathetic overactivity and hypertension in a number of animal models of monogenic and diet-induced obesity74–77.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [76]
Central administration of a leptin receptor antagonist normalizes arterial pressure and renal sympathetic activity in obese rabbits.
“The effectiveness of central administration of a leptin receptor antagonist in normalizing arterial pressure and renal sympathetic activity in obese rabbits provide direct evidence regarding the importance of leptin in driving hypertension and sympathetic overactivity in obesity (50).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [50]
Central administration of an insulin receptor antagonist to obese rabbits decreased arterial pressure, but with no concomitant change in renal sympathetic traffic.
“Notably, central administration of an insulin receptor antagonist to obese rabbits also decreased arterial pressure, but with no concomitant change in renal sympathetic traffic (50).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [50]
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- Authors
- Lim, K., Burke, S. L., & Head, G. A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- ORCID
- Head, Geoffrey A.
- Venue
- Hypertension
- Published
- 2013-03
- Volume
- 61
- Issue
- 3
- Pages
- 628-634
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2096239442
- Cited by
- 95
- References
- 31
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 14 · 2019: 10 · 2018: 2 · 2017: 8 · 2016: 14 · 2015: 10 · 2014: 11 · 2013: 8
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- State Government of Victoria
- Medical Research Council
- National Health and Medical Research Council (1002186, 526618)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- obesity-related hypertension, high-fat diet, leptin, insulin, renal sympathetic nerve activity, central nervous system, leptin antagonist, insulin antagonists, intracerebroventricular administration, blood pressure regulation, rabbits
- MeSH terms
- Animals, Antihypertensive Agents, Blood Pressure, Heart Rate, Hypertension, Insulin, Insulin Antagonists, Kidney, Male, Obesity, Rabbits, Sympathetic Nervous System, Signal Transduction, Leptin, Diet, High-Fat
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