The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Control of Blood Pressure, Appetite, and Glucose by Leptin in Mice Lacking Leptin Receptors in Proopiomelanocortin Neurons
Open accessAbstract
Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR flox/flox /POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR flox/flox /POMC-Cre, wild-type, LepR flox/flox , and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR flox/flox /POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR flox/flox , and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR flox/flox /POMC-Cre mice had normal MAP and heart rate compared with LepR flox/flox but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR flox/flox /POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR flox/flox /POMC-Cre mice. Leptin increased oxygen consumption in LepR flox/flox /POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.
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“Disruption of leptin receptor signaling in POMC neurons abolished the ability of exogenous leptin administration to increase blood pressure (39;41) which provides additional support to the notion that leptin is a critical hormone in coupling hypertension and obesity (Figure 1).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [39]
In the citing paper
“Selective LepR deletion in POMC neurons of the ARC and brainstem also abolished BP increases in mice during chronic leptin infusions140.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [140]
In the citing paper
“In fact, deletion of LepR only in POMC neurons, a major type of neuron in the ARC, prevents increased BP during chronic hyperleptinemia97.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [97]
In the citing paper
“Leptin receptor (LR) deletion specifically in POMC neurons completely abolished the chronic effects of leptin to raise BP and to reduce plasma glucose and insulin levels but did not markedly attenuate the effects of leptin on food intake [50].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [50]
In the citing paper
“These findings suggest that LR activation in POMC neurons is critical for leptin’s ability to increase BP and improve glucose homeostasis but not for its effect to reduce food intake.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [50]
In the citing paper
“Leptin requires activation of POMC neurons and MC4R to mediate its effects on renal SNS activity and BP [28, 50, 51].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [50]
In the citing paper
“Leptin receptor (LR) deletion specifically in POMC neurons completely abolished the chronic effects of leptin to raise BP and to reduce plasma glucose and insulin levels but did not markedly attenuate the effects of leptin on food intake [50].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [50]
In the citing paper
“Similarly, mice lacking leptin signaling in POMC neurons or in the arcuate nucleus of the hypothalamus, where most POMC neurons reside, through deletion of the leptin receptor itself (39;40) or components of its signaling pathway such as the signal transducer and activator of transcription-3 (41) are protected against obesity-associated hypertension.”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [39]
In the citing paper
“Disruption of leptin receptor signaling in POMC neurons abolished the ability of exogenous leptin administration to increase blood pressure (39;41) which provides additional support to the notion that leptin is a critical hormone in coupling hypertension and obesity (Figure 1).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [39]
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Citations
Cites
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A frameshift mutation in human MC4R is associated with a dominant form of obesity
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Phenotypes of Mouse diabetes and Rat fatty Due to Mutations in the OB (Leptin) Receptor
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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
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
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
Self-citationRole of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited
da Silva, A. A., do Carmo, J. M., Li, X., Wang, Z., Mouton, A. J., & Hall, J. E. (2020) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2020.02.066 · Cited by 392
Self-citationLeptin Mediates the Increase in Blood Pressure Associated with Obesity
Simonds, S. E., Pryor, J. T., Ravussin, É., Greenway, F. L., Dileone, R., Allen, A. M., Bassi, J. K., Elmquist, J. K., Keogh, J. M., Henning, E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.058 · Cited by 352
Metadata
- Authors
- do Carmo, J. M., da Silva, A. A., Cai, Z., Lin, S., Dubinion, J. H., & Hall, J. E.
- Affiliations
- From the Departments of Physiology and Biophysics (J.M.d.C., A.A.d.S., J.H.D., J.E.H.) and Pediatrics (Z.C., S.L.), University of Mississippi Medical Center, Jackson, MS.
- University of Mississippi Medical Center (US)
- Venue
- Hypertension
- Published
- 2011-05
- Volume
- 57
- Issue
- 5
- Pages
- 918-926
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC3092393
- OpenAlex
- W1975214074
- Cited by
- 127
- References
- 34
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 2 · 2021: 9 · 2020: 13 · 2019: 6 · 2018: 10 · 2017: 18 · 2016: 11 · 2015: 8 · 2014: 12 · 2013: 15 · 2012: 10
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL051971)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, leptin receptor, proopiomelanocortin neurons, melanocortin system, blood pressure regulation, appetite, glucose regulation, insulin, oxygen consumption, energy balance, metabolic syndrome, hyperleptinemia, hyperglycemia, heart rate
- MeSH terms
- Analysis of Variance, Animals, Appetite, Blood Glucose, Blood Pressure, Body Weight, Eating, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Immunohistochemistry, Insulin, Male, Motor Activity, Neurons, Oxygen Consumption, Pro-Opiomelanocortin, Telemetry, Mice, Knockout, Leptin, Mice, Receptors, Leptin
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