Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice
Abstract
OBJECTIVE: Recent advances in understanding the neuroendocrine pathways regulating appetite, metabolism and body weight afford an opportunity to explore further the mechanisms by which obesity influences arterial pressure. ob/ob(Lep(ob)/Lep(ob)) mice have a mutation in the ob gene and are leptin-deficient. Leptin possesses pressor actions and has been shown to increase arterial pressure when infused chronically or over-expressed transgenically. In contrast, agouti yellow obese(Ay) mice have overexpression of an agouti peptide that blocks melanocortin receptors. Stimulation of melanocortin receptors by alpha-melanocyte-stimulating hormone decreases arterial pressure. DESIGN AND METHODS: This study measured arterial pressure in leptin-deficient ob/ob mice, agouti yellow obese mice and their lean controls to test the hypothesis that the effects of obesity on arterial pressure are importantly influenced by the genetic and neuroendocrine mechanisms causing the obesity. We measured arterial pressure directly in conscious ob/ob mice (n = 14), agouti yellow obese mice (n = 6) and the same number of lean littermates. RESULTS: Body weight was nearly twice as high in ob/ob mice as in their lean controls, but mean arterial pressure was significantly lower in ob/ob mice (92+/-3 mmHg) compared with their lean controls (106+/-2 mmHg; P = 0.00017). In contrast, mean arterial pressure was significantly higher in agouti yellow obese mice (124+/-3 mmHg) than in their lean controls (99+/-1 mmHg; P = 0.000002) despite the fact that the agouti mice had milder obesity. CONCLUSIONS: This study prompts three conclusions: (1) leptin-deficient ob/ob mice and agouti yellow obese mice have contrasting blood pressure responses to obesity, (2) obesity does not invariably increase arterial pressure in mice, and (3) the arterial pressure response to obesity may depend critically on the underlying genetic and neuroendocrine mechanisms.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Leptin-deficient (ob/ob) mice exhibit severe obesity, dyslipidaemia, insulin resistance, and hyperinsulinaemia but reduced blood pressure and sympathetic nerve activity compared with lean control mice.
“In addition, leptin-deficient (ob/ob) mice exhibit severe obesity, dyslipidaemia, insulin resistance and hyperinsulinaemia but reduced BP and SNA compared with lean control mice130.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [130]
Mice with leptin deficiency (ob/ob) have severe obesity, insulin resistance, hyperinsulinemia, and dyslipidemia but lower BP and reduced SNS activity compared to lean mice.
“Mice with leptin deficiency (ob/ob) mice have severe obesity, insulin resistance, hyperinsulinemia, and dyslipidemia but lower BP and reduced SNS activity compared to lean mice112.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [112]
Another caveat of the ob/ob model for the study of hypertrophy is the presence of low arterial pressure, while the opposite is found in most forms of obesity.
“Another caveat of this model for the study of hypertrophy is the presence of low arterial pressure, while the opposite is found in most forms of obesity (224).”
From Cardiac remodeling in obesity (2008) · cites this paper as [224]
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Role of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154 · see citing works
Banting lecture 1988. Role of insulin resistance in human disease.
Reaven, G. (1988) · Diabetes · doi:10.2337/diabetes.37.12.1595 · Cited by 3,801 · see citing works
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030 · see citing works
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936 · see citing works
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.-M., et al. (1998) · Nature · doi:10.1038/32911 · Cited by 2,346 · see citing works
Body Weight and Mortality among Women
Manson, J. E., Willett, W. C., Stampfer, M. J., Colditz, G. A., Hunter, D. J., Hankinson, S. E., Hennekens, C. H., & Speizer, F. E. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509143331101 · Cited by 2,005 · see citing works
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome
Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., & Cone, R. D. (1997) · Nature · doi:10.1038/385165a0 · Cited by 1,902 · see citing works
A frameshift mutation in MC4R associated with dominantly inherited human obesity
Yeo, G. S. H., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., & O'Rahilly, S. (1998) · Nature Genetics · doi:10.1038/2404 · Cited by 1,159 · see citing works
A leptin missense mutation associated with hypogonadism and morbid obesity
Strobel, A., Issad, T., Camoin, L., Ozata, M., & Strosberg, A. D. (1998) · Nature Genetics · doi:10.1038/ng0398-213 · Cited by 1,158 · see citing works
A frameshift mutation in human MC4R is associated with a dominant form of obesity
Vaisse, C., Clément, K., Guy-grand, B., & Froguel, P. (1998) · Nature Genetics · doi:10.1038/2407 · Cited by 1,091 · see citing works
Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.
Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8878 · Cited by 1,033 · 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
Self-citationStamler, R. (1978) · JAMA · doi:10.1001/jama.240.15.1607 · Cited by 712 · see citing works
Chronic 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
Sympathetic and Cardiorenal Actions of Leptin
Haynes, W. G., Sivitz, W. I., Morgan, D. A., Walsh, S. A., & Mark, A. L. (1997) · Hypertension · doi:10.1161/01.hyp.30.3.619 · Cited by 348 · see citing works
Self-citationRenal Denervation Attenuates the Sodium Retention and Hypertension Associated With Obesity
Kassab, S., Kato, T., Wilkins, F. C., Chen, R., Hall, J. E., & Granger, J. P. (1995) · Hypertension · doi:10.1161/01.hyp.25.4.893 · Cited by 307 · see citing works
The vasodilator action of insulin. Implications for the insulin hypothesis of hypertension.
Anderson, E. A., & Mark, A. L. (1993) · Hypertension · doi:10.1161/01.hyp.21.2.136 · Cited by 242 · see citing works
Self-citationIndependent and Additive Effects of Central POMC and Leptin Pathways on Murine Obesity
Boston, B. A., Blaydon, K. M., Varnerin, J. P., & Cone, R. D. (1997) · Science · doi:10.1126/science.278.5343.1641 · Cited by 239 · see citing works
Donnellan, R. B., & Chetty, R. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.8.773 · Cited by 211 · see citing works
Obesity-Induced Hypertension: New Concepts From the Emerging Biology of Obesity
Mark, A. L., Correia, M., Morgan, D. A., Shaffer, R. A., & Haynes, W. G. (1999) · Hypertension · doi:10.1161/01.hyp.33.1.537 · Cited by 185 · see citing works
Self-citationLi, S.-J., Varga, K., Archer, P., Hruby, V. J., Sharma, S. D., Kesterson, R. A., Cone, R. D., & Kunos, G. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-16-05182.1996 · Cited by 152 · see citing works
Augmentation of renal vasoconstrictor responses to norepinephrine and angiotensinii by leptin.
Osei, S. Y. (1999) · American Journal of Hypertension · doi:10.1016/s0895-7061(99)80101-0 · Cited by 3 · 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
The Kidney, Hypertension, and Obesity
Hall, J. E. (2003) · Hypertension · doi:10.1161/01.hyp.0000052314.95497.78 · Cited by 868 · see citing works
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
Obesity, 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
Obesity-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
Cardiac Lipid Accumulation Associated with Diastolic Dysfunction in Obese Mice
Christoffersen, C., Bollano, E., Lindegaard, M. L. S., Bartels, E. D., Goetze, J. P., Andersen, C. B., & Nielsen, L. B. (2003) · Endocrinology · doi:10.1210/en.2003-0242 · Cited by 375 · see citing works
Mechanisms of Obesity-Associated Cardiovascular and Renal Disease
Hall, J. E., Crook, E. D., Jones, D. W., Wofford, M. R., & Dubbert, P. M. (2002) · The American Journal of the Medical Sciences · doi:10.1097/00000441-200209000-00003 · Cited by 373 · 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
Self-citationLeptin and hyperleptinemia - from friend to foe for cardiovascular function
Ren, J. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1810001 · Cited by 305 · 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
Is obesity a major cause of chronic kidney disease?
Hall, J. E., Henegar, J. R., Dwyer, T. M., Liu, J., da Silva, A. A., Kuo, J. J., & Tallam, L. (2004) · Advances in Renal Replacement Therapy · doi:10.1053/j.arrt.2003.10.007 · Cited by 264 · see citing works
Hypertension: Physiology and Pathophysiology
Hall, J. E., Granger, J. P., do Carmo, J. M., da Silva, A. A., Dubinion, J., George, E., Hamza, S., Speed, J., & Hall, M. E. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110058 · Cited by 232 · see citing works
The renin-angiotensin system and natriuretic peptides in obesity-associated hypertension
Engeli, S., & Sharma, A. M. (2001) · Journal of Molecular Medicine · doi:10.1007/s001090000144 · Cited by 225 · see citing works
The 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
Self-citationSelective 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
Self-citationObesity-associated hypertension and kidney disease
Hall, J. E., Kuo, J. J., da Silva, A. A., de Paula, R. B., Liu, J., & Tallam, L. (2003) · Current Opinion in Nephrology and Hypertension · doi:10.1097/00041552-200303000-00011 · Cited by 187 · 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
Self-citationSelective 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
Self-citationRole of leptin in the cardiovascular and endocrine complications of metabolic syndrome
Correia, M. L. G., & Rahmouni, K. (2006) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00562.x · Cited by 121 · see citing works
Self-citationHypothalamic Melanocortin Receptors and Chronic Regulation of Arterial Pressure and Renal Function
Kuo, J. J., Silva, A. A., & Hall, J. E. (2003) · Hypertension · doi:10.1161/01.hyp.0000048194.97428.1a · Cited by 113 · see citing works
Leptin and the Cardiovascular System
Rahmouni, K. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.225 · Cited by 110 · see citing works
Mechanisms mediating renal sympathetic activation to leptin in obesity
Morgan, D. A., Thedens, D. R., Weiss, R., & Rahmouni, K. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90324.2008 · Cited by 89 · see citing works
Self-citationGreenfield, J. R. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02088.x · Cited by 72 · see citing works
The Sympathetic Nervous System in Obesity Hypertension
Lohmeier, T. E., & Iliescu, R. (2013) · Current Hypertension Reports · doi:10.1007/s11906-013-0356-1 · Cited by 62 · see citing works
“These findings suggest that leptin is a critical link between obesity and hypertension, consistent with seminal studies showing that leptin- or leptin receptor– deficient, obese mice have little or no increase in arterial pressure compared to their lean controls [2, 49].”
Matsumura, K., Tsuchihashi, T., Abe, I., & Iida, M. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03045-7 · Cited by 49 · see citing works
Obesity-related hypertension: Is there a role for selective leptin resistance?
Correia, M. L. G., & Haynes, W. G. (2004) · Current Hypertension Reports · doi:10.1007/s11906-004-0074-9 · Cited by 46 · see citing works
Self-citationDifferential 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
Self-citationdo Carmo, J. M., da Silva, A. A., Rushing, J. S., & Hall, J. E. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00392.2011 · Cited by 39 · 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
Mark, A. L., Correia, M. L. G., Rahmouni, K., & Haynes, W. G. (2004) · Clinical and Experimental Hypertension · doi:10.1081/ceh-200031948 · Cited by 32 · see citing works
Self-citationdo Carmo, J. M., da Silva, A. A., Sessums, P. O., Ebaady, S. H., Pace, B. R., Rushing, J. S., Davis, M. T., & Hall, J. E. (2014) · International Journal of Obesity · doi:10.1038/ijo.2013.177 · Cited by 26 · see citing works
- Authors
- Mark, A. L., Shaffer, R. A., Correia, M. L. G., Morgan, D. A., Sigmund, C. D., & Haynes, W. G.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Mark, Allyn L.
- Venue
- Journal of Hypertension
- Published
- 1999-12
- Volume
- 17
- Issue
- Supplement
- Pages
- 1949-1953
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W1976029372
- Cited by
- 254
- References
- 23
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 8 · 2019: 9 · 2018: 5 · 2017: 12 · 2016: 13 · 2015: 10 · 2014: 14 · 2013: 12 · 2012: 8
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50hl044546-05)
- National Heart, Lung, and Blood Institute (HL-14388, HL-44546, P01HL014388)
- 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
- obesity, blood pressure, leptin deficiency, ob/ob mice, melanocortin receptors, alpha-melanocyte-stimulating hormone, neuroendocrine regulation
- MeSH terms
- Animals, Blood Pressure, Body Weight, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Obesity, Reference Values, Leptin, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
