Role of Proopiomelanocortin Neuron Stat3 in Regulating Arterial Pressure and Mediating the Chronic Effects of Leptin
Open accessAbstract
Although signal transducer and activator of transcription 3 (Stat3) is a key second messenger by which leptin regulates appetite and body weight, its role in specific neuronal populations in metabolic regulation and in mediating the chronic effects of leptin on blood pressure is unknown. The current study tested the hypothesis that Stat3 signaling in proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on mean arterial pressure (MAP), as well as on glucose regulation, energy expenditure, and food intake. Stat3 flox/flox mice were crossed with POMC-Cre mice to generate mice with Stat3 deletion specifically in POMC neurons (Stat3 flox/flox /POMC-Cre). Oxygen consumption (V o 2 ), carbon dioxide respiration (V co 2 ), motor activity, heat production, food intake, and MAP were measured 24 hours/d. After baseline measurements, leptin was infused (4 μg/kg per min, IP) for 7 days. Stat3 flox/flox /POMC-Cre mice were hyperphagic, heavier, and had increased respiratory quotients compared with control Stat3 flox/flox mice. Baseline MAP was not different between the groups, and chronic leptin infusion reduced food intake similarly in both groups (27 versus 29%). V o 2 , V co 2 , and heat production responses to leptin were not significantly different in control and Stat3 flox/flox /POMC-Cre mice. However, leptin-mediated increases in MAP were completely abolished, and blood pressure responses to acute air–jet stress were attenuated in male Stat3 flox/flox /POMC-Cre mice. These results indicate that Stat3 signaling in POMC neurons is essential for leptin-mediated increases in MAP, but not for anorexic or thermogenic effects of leptin.
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Targeted STAT3 deletion in POMC neurons markedly blunted the blood pressure effect of leptin in mice but caused only small reductions in energy expenditure and increases in food intake.
“Targeted STAT3 deletion in POMC neurons markedly blunted the BP effect of leptin in mice but caused only small reductions in energy expenditure and increases in food intake142.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [142]
STAT3 signaling contributes to leptin's chronic effects on BP, and deletion of STAT3 specifically in POMC neurons attenuates leptin's effect to raise BP.
“Deletion of STAT3 specifically in POMC neurons attenuated leptin’s effect to raise BP but had only minor effects on food intake and energy expenditure106.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [106]
Mice lacking leptin signaling in POMC neurons or in the arcuate nucleus of the hypothalamus through deletion of the leptin receptor itself or components of its signaling pathway such as STAT3 are protected against obesity-associated hypertension.
“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 [41]
Leptin is a critical hormone in coupling hypertension and obesity.
“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 [41]
Disruption of leptin receptor signaling in POMC neurons abolished the ability of exogenous leptin administration to increase blood pressure.
“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 [41]
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STAT3 signalling is required for leptin regulation of energy balance but not reproduction
Bates, S. H., Stearns, W. H., Dundon, T. A., Schubert, M., Tso, A. W. K., Wang, Y., Banks, A. S., Lavery, H. J., Haq, A. K., Maratos-Flier, E., et al. (2003) · Nature · doi:10.1038/nature01388 · Cited by 1,010 · see citing works
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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
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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-citationGao, Q., Wolfgang, M. J., Neschen, S., Morino, K., Horvath, T. L., Shulman, G. I., & Fu, X.-Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0303992101 · Cited by 385 · see citing works
Yang, R., & Barouch, L. A. (2007) · Circulation Research · doi:10.1161/circresaha.107.156596 · Cited by 327 · see citing works
Ernst, M. B., Wunderlich, C. M., Hess, S., Paehler, M., Mesaros, A., Koralov, S. B., Kleinridders, A., Husch, A., Münzberg, H., Hampel, B., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5712-08.2009 · Cited by 185 · see citing works
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Xu, A. W., Marie, L. S., Kaelin, C. B., & Barsh, G. S. (2006) · Endocrinology · doi:10.1210/en.2006-1119 · Cited by 165 · see citing works
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- Authors
- Dubinion, J. H., do Carmo, J. M., Adi, A., Hamza, S., da Silva, A. A., & Hall, J. E.
- Affiliations
- University of Mississippi Medical Center (US)
- From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS.
- Venue
- Hypertension
- Published
- 2013-05
- Volume
- 61
- Issue
- 5
- Pages
- 1066-1074
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC3678380
- OpenAlex
- W2013688437
- Cited by
- 31
- References
- 20
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 2
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- School of Medicine, Indiana University
- 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 › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- STAT3 signaling, proopiomelanocortin neurons, leptin, mean arterial pressure, blood pressure regulation, dietary intake, energy expenditure, glucose regulation, hypothalamic neurons
- MeSH terms
- Animals, Appetite, Blood Pressure, Body Weight, Energy Metabolism, Female, Glucose, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Neurons, Oxygen Consumption, Pro-Opiomelanocortin, Sex Factors, Signal Transduction, Leptin, Models, Animal, STAT3 Transcription Factor, Mice
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