Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet
Abstract
OBJECTIVE: Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. METHODS: Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days. RESULTS: High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively). CONCLUSION: These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.
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In rodents, high-fat-diet-induced obesity blunts the acute anorexic effects of leptin but does not cause resistance to the chronic central nervous system effects of leptin on blood pressure or heart rate.
“We found that in rodents, HFD-induced obesity blunts the acute anorexic effects of leptin but does not cause resistance to the chronic CNS effects of leptin on BP or HR137.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [137]
If leptin is administered ICV, bypassing the blood brain barrier, food intake is substantially decreased in obese rodents fed a high fat diet.
“However, if leptin is administered ICV, bypassing the blood brain barrier, food intake is substantially decreased in obese rodents fed a high fat diet101.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [101]
Cites
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326 · see citing works
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., et al. (1995) · Nature Medicine · doi:10.1038/nm1195-1155 · Cited by 3,725 · see citing works
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356 · see citing works
Frederich, R. C., Hamann, A., Anderson, S., Löllmann, B., Lowell, B. B., & Flier, J. S. (1995) · Nature Medicine · doi:10.1038/nm1295-1311 · Cited by 1,660 · see citing works
Receptor-mediated regional sympathetic nerve activation by leptin.
Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119532 · Cited by 979 · see citing works
The Kidney, Hypertension, and Obesity
Hall, J. E. (2003) · Hypertension · doi:10.1161/01.hyp.0000052314.95497.78 · Cited by 868 · see citing works
Self-citationChronic Leptin Infusion Increases Arterial Pressure
Shek, E. W., Brands, M. W., & Hall, J. E. (1998) · Hypertension · doi:10.1161/01.hyp.31.1.409 · Cited by 686 · see citing works
Self-citationObesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins
Hall, J. E., da Silva, A. A., do Carmo, J. M., Dubinion, J., Hamza, S., Munusamy, S., Smith, G., & Stec, D. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.113175 · Cited by 528 · see citing works
Self-citationDunbar, J. C., Hu, Y., & Lu, H. (1997) · Diabetes · doi:10.2337/diab.46.12.2040 · Cited by 414 · see citing works
Yang, R., & Barouch, L. A. (2007) · Circulation Research · doi:10.1161/circresaha.107.156596 · Cited by 327 · see citing works
Role of Selective Leptin Resistance in Diet-Induced Obesity Hypertension
Rahmouni, K., Morgan, D. A., Morgan, G. M., Mark, A. L., & Haynes, W. G. (2005) · Diabetes · doi:10.2337/diabetes.54.7.2012 · Cited by 319 · see citing works
Chronic Cardiovascular and Renal Actions of Leptin: Role of Adrenergic Activity
Carlyle, M., Jones, O. B., Kuo, J. J., & Hall, J. E. (2002) · Hypertension · doi:10.1161/hy0202.104398 · Cited by 292 · see citing works
Self-citationThe Concept of Selective Leptin Resistance
Correia, M. L. G., Haynes, W. G., Rahmouni, K., Morgan, D. A., Sivitz, W. I., & Mark, A. L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.439 · Cited by 218 · see citing works
Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications
Mark, A. L., Correia, M. L. G., Rahmouni, K., & Haynes, W. G. (2002) · Journal of Hypertension · doi:10.1097/00004872-200207000-00001 · Cited by 215 · see citing works
Widdowson, P. S., Upton, R., Buckingham, R. E., Arch, J. R. S., & Williams, G. (1997) · Diabetes · doi:10.2337/diab.46.11.1782 · Cited by 210 · see citing works
Leptin Acts in the Central Nervous System to Produce Dose-Dependent Changes in Arterial Pressure
Correia, M., Morgan, D. A., Sivitz, W. I., Mark, A. L., & Haynes, W. G. (2001) · Hypertension · doi:10.1161/01.hyp.37.3.936 · Cited by 146 · see citing works
Selective Resistance to Central Neural Administration of Leptin in Agouti Obese Mice
Rahmouni, K., Haynes, W. G., Morgan, D. A., & Mark, A. L. (2002) · Hypertension · doi:10.1161/hy0202.102836 · Cited by 126 · see citing works
da Silva, A. A., Kuo, J. J., & Hall, J. E. (2004) · Hypertension · doi:10.1161/01.hyp.0000128421.23499.b9 · Cited by 117 · see citing works
Self-citationda Silva, A. A., do Carmo, J. M., Kanyicska, B., Dubinion, J., Brandon, E., & Hall, J. E. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.100636 · Cited by 79 · see citing works
Self-citationda Silva, A. A., do Carmo, J. M., Freeman, J. N., Tallam, L. S., & Hall, J. E. (2009) · Diabetes · doi:10.2337/db08-1221 · Cited by 47 · see citing works
Self-citationda Silva, A. A., Kuo, J. J., Tallam, L. S., Liu, J., & Hall, J. E. (2005) · Hypertension · doi:10.1161/01.hyp.0000198458.70351.e0 · Cited by 33 · see citing works
Self-citationDubinion, J. H., da Silva, A. A., & Hall, J. E. (2010) · Journal of Hypertension · doi:10.1097/hjh.0b013e328339f20e · Cited by 24 · see citing works
Self-citationCrossing the Border: Developmental Regulation of Leptin Transport to the Brain
Bouret, S. G. (2008) · Endocrinology · doi:10.1210/en.2007-1698 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2015) · Circulation Research · doi:10.1161/circresaha.116.305697 · Cited by 1,360 · see citing works
Self-citationObesity, kidney dysfunction and hypertension: mechanistic links
Hall, J. E., do Carmo, J. M., da Silva, A. A., Wang, Z., & Hall, M. E. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0145-4 · Cited by 654 · see citing works
Self-citationObesity, hypertension, and chronic kidney disease
Hall, J., Juncos, L., Wang, Z., Hall, M., do Carmo, J., & da Silva, A. (2014) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s39739 · Cited by 520 · see citing works
Self-citationObesity, kidney dysfunction, and inflammation: interactions in hypertension
Hall, J. E., Mouton, A. J., da Silva, A. A., Omoto, A. C. M., Wang, Z., Li, X., & do Carmo, J. M. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa336 · Cited by 279 · see citing works
Self-citationTissue-Specific Effects of Leptin on Glucose and Lipid Metabolism
Pereira, S., Cline, D. L., Glavas, M. M., Covey, S. D., & Kieffer, T. J. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa027 · Cited by 247 · see citing works
Selective leptin resistance revisited
Mark, A. L. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00180.2013 · Cited by 162 · see citing works
Xue, B., Yu, Y., Zhang, Z., Guo, F., Beltz, T. G., Thunhorst, R. L., Felder, R. B., & Johnson, A. K. (2016) · Hypertension · doi:10.1161/hypertensionaha.115.06736 · Cited by 100 · see citing works
Mechanisms and treatment of obesity-related hypertension—Part 1: Mechanisms
Parvanova, A. I., Reseghetti, E., Abbate, M., & Ruggenenti, P. L. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad282 · Cited by 98 · see citing works
Leptin and cardiovascular diseases
Hou, N., & Luo, J. (2011) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2011.05619.x · Cited by 79 · see citing works
Obesity-Induced Hypertension: Brain Signaling Pathways
do Carmo, J. M., da Silva, A. A., Wang, Z., Fang, T., Aberdein, N., Rodriguez, C. E. P. D. L., & Hall, J. E. (2016) · Current Hypertension Reports · doi:10.1007/s11906-016-0658-1 · Cited by 64 · see citing works
Self-citationSmith, C. E., Mollard, R. C., Luhovyy, B. L., & Anderson, G. H. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512000700 · Cited by 60 · see citing works
Leptin and its cardiovascular effects: Focus on angiogenesis
Khazaei, M., & Tahergorabi, Z. (2015) · Advanced Biomedical Research · doi:10.4103/2277-9175.156526 · Cited by 51 · see citing works
A Novel Adipocytokine, Omentin, Inhibits Agonists-Induced Increases of Blood Pressure in Rats
Kazama, K., Okada, M., Hara, Y., & Yamawaki, H. (2013) · Journal of Veterinary Medical Science · doi:10.1292/jvms.12-0537 · Cited by 36 · see citing works
Cardiovascular Actions of Leptin in the Subfornical Organ are Abolished by Diet‐Induced Obesity
Smith, P., & Ferguson, A. V. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02257.x · Cited by 34 · see citing works
Li, B., Shi, Z., Cassaglia, P. A., & Brooks, V. L. (2013) · Hypertension · doi:10.1161/hypertensionaha.111.00518 · Cited by 34 · see citing works
Obesity Hypertension: Pathophysiological Role of Leptin in Neuroendocrine Dysregulation
Go, O., Liu, K., Villarreal, D., Spear, R. M., Freeman, R. H., Reams, G. P., & Weber, K. T. (2013) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31827ad5cf · Cited by 22 · see citing works
Özbek, L., Abdel‐Rahman, S. M., Unlu, S., Güldan, M., Copur, S., Burlacu, A., Covic, A. C., & Kanbay, M. (2024) · Medicina · doi:10.3390/medicina60101668 · Cited by 22 · see citing works
Modulation of the cardiovascular system by leptin
Abel, E. D., & Sweeney, G. (2012) · Biochimie · doi:10.1016/j.biochi.2012.03.019 · Cited by 22 · see citing works
Messenger, S. A., Moreau, J. M., & Ciriello, J. (2013) · Brain Research · doi:10.1016/j.brainres.2013.03.022 · Cited by 18 · see citing works
Animal Models in Obesity and Hypertension
Segal‐Lieberman, G., & Rosenthal, T. (2013) · Current Hypertension Reports · doi:10.1007/s11906-013-0338-3 · Cited by 17 · see citing works
Habeeballah, H. H., Alsuhaymi, N., Stebbing, M. J., Jenkins, T. A., & Badoer, E. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2016.00672 · Cited by 9 · see citing works
Guo, D., Luo, Z., Olson, A., Morgan, D. A., Newell, E. A., & Rahmouni, K. (2025) · Metabolism · doi:10.1016/j.metabol.2025.156387 · Cited by 1 · see citing works
Leptin, the Autonomic Nervous System, and Hypertension
da Silva, A. A., do Carmo, J. M., Wang, Z., & Hall, J. E. (2014) · Springer eBooks · doi:10.1007/978-3-319-09915-6_14 · Cited by 1 · see citing works
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Messenger, S. A. (2013) · Scholarship@Western (Western University)
THE SUBFORNICAL ORGAN AND AREA POSTREMA MEDIATE THE CENTRAL EFFECTS OF CIRCULATING LEPTIN
Smith, P. (2012) · QSpace (Queen's University Library)
Leptin and cardiovascular health
Pereira, S. X. E. R. L. (2026) · Endocrinology · doi:10.1210/endocr/bqag050
The onset of hypertension in metabolic syndrome is independent of renal sympathetic innervation
Flores‐Sandoval, O., Cárdenas‐Romero, S., Báez‐Ruíz, A., Salgado‐Delgado, R., & Saderi, N. (2026) · Life Science Alliance · doi:10.26508/lsa.202503568
- Authors
- Dubinion, J. H., da Silva, A. A., & Hall, J. E.
- Affiliations
- University of Mississippi Medical Center (US)
- Corresponding author
- Dubinion, John H
- ORCID
- Hall, John E
- Venue
- Journal of Hypertension
- Published
- 2011-04
- Volume
- 29
- Issue
- 4
- Pages
- 758-762
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W2332505512
- Cited by
- 27
- References
- 23
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 7 · 2012: 3
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01-HL-51971, P01HL051971)
- 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 › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- leptin resistance, high-fat diet, obesity, intracerebroventricular infusion, blood pressure, heart rate, appetite, dietary intake, sympathetic activity
- MeSH terms
- Animals, Appetite, Blood Pressure, Body Weight, Dietary Fats, Feeding Behavior, Injections, Intraventricular, Rats, Sprague-Dawley, Leptin, Rats
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