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Receptor-mediated regional sympathetic nerve activation by leptin.
Open accessAbstract
Leptin is a peptide hormone produced by adipose tissue which acts centrally to decrease appetite and increase energy expenditure. Although leptin increases norepinephrine turnover in thermogenic tissues, the effects of leptin on directly measured sympathetic nerve activity to thermogenic and other tissues are not known. We examined the effects of intravenous leptin and vehicle on sympathetic nerve activity to brown adipose tissue, kidney, hindlimb, and adrenal gland in anesthetized Sprague-Dawley rats. Intravenous infusion of mouse leptin over 3 h (total dose 10-1,000 microg/kg) increased plasma concentrations of immunoreactive murine leptin up to 50-fold. Leptin slowly increased sympathetic nerve activity to brown adipose tissue (+286+/-64% at 1,000 microg/kg; P = 0.002). Surprisingly, leptin infusion also produced gradual increases in renal sympathetic nerve activity (+228+/-63% at 1,000 microg/kg; P = 0.0008). The effect of leptin on sympathetic nerve activity was dose dependent, with a threshold dose of 100 microg/kg. Leptin also increased sympathetic nerve activity to the hindlimb (+287+/-60%) and adrenal gland (388+/-171%). Despite the increase in overall sympathetic nerve activity, leptin did not increase arterial pressure or heart rate. Leptin did not change plasma glucose and insulin concentrations. Infusion of vehicle did not alter sympathetic nerve activity. Obese Zucker rats, known to possess a mutation in the gene for the leptin receptor, were resistant to the sympathoexcitatory effects of leptin, despite higher achieved plasma leptin concentrations. These data demonstrate that leptin increases thermogenic sympathetic nerve activity and reveal an unexpected stimulatory effect of leptin on overall sympathetic nerve traffic.
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In the citing paper
“These findings are in contrast to the effect of leptin administration on increase natriuresis (49, 50) and sympathetic activity (51) in normal, nonobese leptin-resistant Zucker rats (51).”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [51]
Experimental — accuracy not yet measuredIn the citing paper
“Plasma leptin concentration is highly correlated with SNA activity123, and acute leptin infusions increase SNA in the brown adipose tissue, adrenal glands and kidneys of rodents124.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [124]
In the citing paper
“acute leptin administration in rodents increased SNS activity in brown adipose tissue (BAT), the adrenal gland, and the kidneys84.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [84]
In the citing paper
“Acute leptin administration in rodents and humans increases renal and muscle SNS activity [45, 46] while chronic increases in plasma leptin levels, comparable to those found in severe obesity, caused sustained increases in BP and HR in rodents despite causing weight loss which would normally reduce BP [47].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [45]
In the citing paper
“In addition its effects on appetite and metabolism, leptin acts in the brain to produce receptor-mediated increases in regional sympathetic activity91.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [91]
In the citing paper
“Leptin is a potent appetite suppressant and, like insulin, stimulates the SNS.24,25”
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Citations
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
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
Weight-Reducing Effects of the Plasma Protein Encoded by the obese Gene
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., & Friedman, J. M. (1995) · Science · doi:10.1126/science.7624777 · Cited by 4,451
Effects of the obese Gene Product on Body Weight Regulation in ob / ob Mice
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T., & Collins, F. (1995) · Science · doi:10.1126/science.7624776 · Cited by 4,017
Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995) · Science · doi:10.1126/science.7624778 · Cited by 3,243
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117
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
Identification of targets of leptin action in rat hypothalamus.
Schwartz, M. W., Seeley, R. J., Campfield, L. A., Burn, P., & Baskin, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118891 · Cited by 1,499
Leptin enters the brain by a saturable system independent of insulin
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., & Maness, L. M. (1996) · Peptides · doi:10.1016/0196-9781(96)00025-3 · Cited by 1,222
Cited by
Sorted by citations
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433
Leptin and the regulation of body weight in mammals
Friedman, J. M., & Halaas, J. L. (1998) · Nature · doi:10.1038/27376 · Cited by 5,405
“Direct measurement of nerve activity has indicated that infusion of leptin increases sympathetic activity to brown adipose tissue, kidney, hind limb and adrenal glan”
BackgroundLeptin 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
“In addition to regulating long-term energy balance, leptin also rapidly affects neuronal activit”
BackgroundLeptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
“In support of the first mechanism, peripheral leptin injection increases sympathetic nerve activity that innervates hindlimb”
BackgroundTowards a molecular understanding of adaptive thermogenesis
Lowell, B. B., & Spiegelman, B. M. (2000) · Nature · doi:10.1038/35007527 · Cited by 1,630
“Leptin administration, either centrally or peripherally, increases sympathetic nerve activity to brown fa”
BackgroundObesity-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
Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ
Trayhurn, P., & Beattie, J. H. (2001) · Proceedings of The Nutrition Society · doi:10.1079/pns200194 · Cited by 1,292
Signals That Regulate Food Intake and Energy Homeostasis
Woods, S. C., Seeley, R. J., Porte, D., & Schwartz, M. W. (1998) · Science · doi:10.1126/science.280.5368.1378 · Cited by 1,177
Do stress reactions cause abdominal obesity and comorbidities?
Björntorp, P. A. (2001) · Obesity Reviews · doi:10.1046/j.1467-789x.2001.00027.x · Cited by 1,160
“This is of interest because there is recent evidence that leptin activates the central sympathetic nervous system, followed by elevated blood pressure (67).”
BackgroundLeptin and Obesity: Role and clinical implication.
Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T., & Isenovic, E. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.585887 · Cited by 1,121
Fructose, weight gain, and the insulin resistance syndrome,,
Elliott, S. S., Keim, N. L., Stern, J. S., Teff, K. L., & Havel, P. J. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.5.911 · Cited by 1,031
Leptin: a review of its peripheral actions and interactions
Margetic, S., Gazzola, C., Pegg, G. G., & Hill, R. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0802142 · Cited by 1,022
Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome
Fernández-Real, J. M., & Ricart, W. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0010 · Cited by 886
Wolf, G., Chen, S., Han, D. C., & Ziyadeh, F. N. (2002) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2002.29865 · Cited by 870
Leptin Activates Hypothalamic CART Neurons Projecting to the Spinal Cord
Elias, C. F., Lee, C., Kelly, J., Aschkenasi, C. J., Ahima, R. S., Couceyro, P. R., Kuhar, M. J., Saper, C. B., & Elmquist, J. K. (1998) · Neuron · doi:10.1016/s0896-6273(00)80656-x · Cited by 809
Progress and Challenges in Metabolic Syndrome in Children and Adolescents
Steinberger, J., Daniels, S. R., Eckel, R. H., Hayman, L. L., Lustig, R. H., McCrindle, B. W., & Mietus‐Snyder, M. (2009) · Circulation · doi:10.1161/circulationaha.108.191394 · Cited by 721
Sympathetic Nervous System Overactivity and Its Role in the Development of Cardiovascular Disease
Malpas, S. C. (2010) · Physiological Reviews · doi:10.1152/physrev.00007.2009 · Cited by 696
Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism
Park, H. K., & Ahima, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.08.004 · Cited by 710
“In rodents, leptin stimulates brown adipose tissue (BAT) thermogenesis by increasing the expression of uncoupling protein (UCP)-1 [41, 42].”
Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications
Kelesidis, T., Kelesidis, I., Chou, S. H.-H., & Mantzoros, C. S. (2010) · Annals of Internal Medicine · doi:10.7326/0003-4819-152-2-201001190-00008 · Cited by 693
“In mice, leptin increases sympathetic nerve activity (27) and activates brown adipose tissue thermogenesis (28, 29); these effects have not been confirmed in humans (30).”
BackgroundObesity, 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
Weight Loss and the Renin-Angiotensin-Aldosterone System
Engeli, S., Böhnke, J., Gorzelniak, K., Janke, J., Schling, P., Bäder, M., Luft, F. C., & Sharma, A. M. (2005) · Hypertension · doi:10.1161/01.hyp.0000154361.47683.d3 · Cited by 627
The Sympathetic Nervous System Alterations in Human Hypertension
Grassi, G., Mark, A., & Esler, M. (2015) · Circulation Research · doi:10.1161/circresaha.116.303604 · Cited by 616
“acts in the brain to produce receptor-mediated increases in regional sympathetic activity.(90) A large body of evidence has”
BackgroundSelf-citationBjörntorp, P. A., & Rosmond, R. (2000) · Nutrition · doi:10.1016/s0899-9007(00)00422-6 · Cited by 584
Chan, J. L., Heist, K., DePaoli, A. M., Veldhuis, J. D., & Mantzoros, C. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17490 · Cited by 697
“These findings are in contrast to the effect of leptin administration on increase natriuresis (49, 50) and sympathetic activity (51) in normal, nonobese leptin-resistant Zucker rats (51).”
ResultNew insights into sympathetic regulation of glucose and fat metabolism
Nonogaki, K. (2000) · Diabetologia · doi:10.1007/s001250051341 · Cited by 589
“In addition, i. v. infusion of leptin has been shown to gradually increase sympathetic nerve activity in brown adipose tissue, kidney, hindlimb and adrenal medulla [ 73 ].”
BackgroundRosenbaum, M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25977 · Cited by 575
Fatty acids, lipotoxicity and insulin secretion
McGarry, J., & Dobbins, R. L. (1999) · Diabetologia · doi:10.1007/s001250051130 · Cited by 548
Unraveling the central nervous system pathways underlying responses to leptin
Elmquist, J. K., Maratos-Flier, E., Saper, C. B., & Flier, J. S. (1998) · Nature Neuroscience · doi:10.1038/2164 · Cited by 520
Landsberg, L., Aronne, L. J., Beilin, L. J., Burke, V., Igel, L. I., Lloyd‐Jones, D., & Sowers, J. (2013) · The Journal of Clinical Hypertension · doi:10.1111/jch.12049 · Cited by 528
“Leptin, the polypeptide product of the ob ⁄ ob gene, is produced in adipocytes and secreted into plasma where the circulating concentration reflects the fat mass of the individual.23 Leptin is a potent appetite suppressant and, like insulin, stimulates the SNS.24,25 Although leptin deficiency causes severe obesity in…”
BackgroundLeptin-specific patterns of gene expression in white adipose tissuePreprint
Soukas, A. A., Cohen, P., Socci, N. D., & Friedman, J. M. (2000) · Genes & Development · doi:10.1101/gad.14.8.963 · Cited by 513
“The nature of the efferent signals from the CNS that regulate metabolism in response to leptin are not well characterized, although some evidence suggests that the sympathetic nervous system may play a role (Collins et al. 1996; Dunbar et al. 1997; Haynes et al. 1997; Elmquist et al. 1999).”
BackgroundThe AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
Viollet, B., Andreelli, F., Jørgensen, S. B., Perrin, C., Geloen, A., Flamez, D., Mu, J., Lenzner, C., Baud, O., Bennoun, M., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16567 · Cited by 499
The selfish brain: Competition for energy resources
Peters, A., Schweiger, U., Pellerin, L., Hubold, C., Oltmanns, K. M., Conrad, M., Schultes, B., Born, J., & Fehm, H. L. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.03.002 · Cited by 489
Havel, P. J. (2001) · Experimental Biology and Medicine · doi:10.1177/153537020122601102 · Cited by 486
Pathophysiological role of leptin in obesity-related hypertension
Aizawa-Abe, M., Ogawa, Y., Masuzaki, H., Ebihara, K., Satoh, N., Iwai, H., Matsuoka, N., Hayashi, T., Hosoda, K., Inoue, G., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8341 · Cited by 477
The cellular and molecular bases of leptin and ghrelin resistance in obesity
Cui, H., López, M., & Rahmouni, K. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.222 · Cited by 498
Leptin and Cardiovascular Disease
Koh, K. K., Park, S. M., & Quon, M. J. (2008) · Circulation · doi:10.1161/circulationaha.107.741645 · Cited by 481
Modulation of Blood Pressure by Central Melanocortinergic Pathways
Greenfield, J. R., Miller, J. W., Keogh, J. M., Henning, E., Satterwhite, J. H., Cameron, G. S., Astruc, B., Mayer, J. P., Brage, S., See, T. C., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0803085 · Cited by 477
Chin, K., Shimizu, K., Nakamura, T., Narai, N., Masuzaki, H., Ogawa, Y., Mishima, M., Nakamura, T., Nakao, K., & Ohi, M. (1999) · Circulation · doi:10.1161/01.cir.100.7.706 · Cited by 450
Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea
Phillips, B. G., Kato, M., Narkiewicz, K., Choe, I., & Somers, V. K. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.1.h234 · Cited by 430
“Animal studies demonstrate that leptin infusion results in sympathetic activation and tachycardia (4, 6, 15).”
BackgroundCentral Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure
Morrison, S. F., Madden, C. J., & Tupone, D. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.007 · Cited by 437
“…a permissive signal, ad libitum-fed animals, particularly in a thermoneutral environment, may have little BAT response to exogenous leptin (Sivitz et al., 1999), although supraphysiological levels of leptin have been effective in other studies on fed animals (Haynes et al., 1997; Morrison, 2004).”
BackgroundLeptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei
Elmquist, J. K., Ahima, R. S., Elias, C. F., Flier, J. S., & Saper, C. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.2.741 · Cited by 376
Regulation of Body Weight in Humans
Jéquier, E., & Tappy, L. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.2.451 · Cited by 379
“The autonomic nervous system is also implicated in this efferent limb; leptin increases sympathetic nervous system (SNS) activity (109), which mediates its action on energy expenditure, whereas NPY, acting on the paraventricular nucleus (PVN) NPY receptors, reduces SNS outflow to brown adipose tissue (13).”
BackgroundSixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367
Role 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
Shariq, O. A., & McKenzie, T. J. (2020) · Gland Surgery · doi:10.21037/gs.2019.12.03 · Cited by 427
“Although leptin infusions in animal models have been shown to stimulate SNS activity and lead to an increase in BP (64,65), the administration of recombinant leptin for 12 weeks in overweight or obese humans had no effect on BP (66).”
BackgroundInteractions between the melanocortin system and leptin in control of sympathetic nerve traffic
Haynes, W. G., Morgan, D. A., Djalali, A., Sivitz, W. I., & Mark, A. L. (1999) · Hypertension · doi:10.1161/01.hyp.33.1.542 · Cited by 358
Leptin is associated with increased risk of myocardial infarction
Söderberg, S., Åhrén, B., Jansson, J., Johnson, O., Hallmans, G., Asplund, K., & Olsson, T. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00571.x · Cited by 356
The Physiology of Obese-Hyperglycemic Mice [ob/obMice]
Lindström, P. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.117 · Cited by 372
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 351
Self-citationFever and hypothermia in systemic inflammation: recent discoveries and revisions
Romanovsky, A. A. (2005) · Frontiers in bioscience · doi:10.2741/1690 · Cited by 345
Barouch, L. A., Berkowitz, D. E., Harrison, R. W., O’Donnell, C. P., & Hare, J. M. (2003) · Circulation · doi:10.1161/01.cir.0000083716.82622.fd · Cited by 341
Diepvens, K., Westerterp, K. R., & Westerterp‐Plantenga, M. S. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00832.2005 · Cited by 344
“could be increased leptin release from larger fat depots, an endocrine signal known to increase sympathetic activity via hypothalamic mechanisms in rats (54, 55) (see below).”
BackgroundHavel, P. J. (2000) · Proceedings of The Nutrition Society · doi:10.1017/s0029665100000410 · Cited by 330
“Accordingly, leptin administration increases the firing rate of sympathetic nerves innervating several tissues in rodents (Haynes et al. 1997) and increases circulating noradrenaline concentrations in non-human primates (Tang-Christensen et al. 1999a).”
BackgroundVecchione, C., Maffei, A., Colella, S., Aretini, A., Poulet, R., Frati, G., Gentile, M. T., Fratta, L., Trimarco, V., Trimarco, B., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.1.168 · Cited by 331
Effect of leptin on allergic airway responses in mice
Shore, S. A., Schwartzman, I. N., Mellema, M. S., Flynt, L., Imrich, A., & Johnston, R. A. (2005) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2004.10.007 · Cited by 330
Leptin induces direct vasodilation through distinct endothelial mechanisms.
Lembo, G., Vecchione, C., Fratta, L., Marino, G., Trimarco, V., d’Amati, G., & Trimarco, B. (2000) · Diabetes · doi:10.2337/diabetes.49.2.293 · Cited by 329
Model for the regulation of energy balance and adiposity by the central nervous system
Schwartz, M. W., Baskin, D. G., Kaiyala, K. J., & Woods, S. C. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.4.584 · Cited by 325
Hypothalamic nutrient sensing in the control of energy homeostasis
Blouet, C., & Schwartz, G. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.024 · Cited by 343
“[72] Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI.”
BackgroundRole 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
Self-citationOldfield, B. J., Giles, M., Watson, A. M. D., Anderson, C. R., Colvill, L. M., & McKinley, M. J. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00555-3 · Cited by 317
Leggio, M., Lombardi, M., Caldarone, E., Severi, P., D’Emidio, S., Armeni, M., Bravi, V., Bendini, M. G., & Mazza, A. (2017) · Hypertension Research · doi:10.1038/hr.2017.75 · Cited by 319
Type 2 Diabetes Mellitus and Hypertension
Lastra, G., Syed, S., Kurukulasuriya, L. R., Manrique, C., & Sowers, J. R. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.09.005 · Cited by 307
Landsberg, L. (2001) · Journal of Hypertension · doi:10.1097/00004872-200103001-00001 · Cited by 312
Insulin resistance and the metabolic syndrome
Landsberg, L. (2005) · Diabetologia · doi:10.1007/s00125-005-1818-z · Cited by 309
Leptin and hyperleptinemia - from friend to foe for cardiovascular function
Ren, J. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1810001 · Cited by 305
“It should be mentioned that acute leptin administration does not consistently elicit a hypertensive effect ( Haynes et al. 1997, Shirasaka et al. 2003).”
BackgroundInfluentialThe metabolic syndrome — a neuroendocrine disorder?
Björntorp, P. A., & Rosmond, R. (2000) · British Journal Of Nutrition · doi:10.1017/s0007114500000957 · Cited by 295
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
Leptin and brain–adipose crosstalks
Caron, A., Lee, S., Elmquist, J. K., & Gautron, L. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.7 · Cited by 284
Landsberg, L., Aronne, L. J., Beilin, L. J., Burke, V., Igel, L. I., Lloyd‐Jones, D. M., & Sowers, J. R. (2012) · Obesity · doi:10.1002/oby.20181 · Cited by 296
“Leptin, the polypeptide product of the ob ⁄ ob gene, is produced in adipocytes and secreted into plasma where the circulating concentration reflects the fat mass of the individual.23 Leptin is a potent appetite suppressant and, like insulin, stimulates the SNS.24,25 Although leptin deficiency causes severe obesity in…”
BackgroundAugmented Placental Production of Leptin in Preeclampsia: Possible Involvement of Placental Hypoxia
Mise, H., Sagawa, N., Matsumoto, T., Yura, S., Nanno, H., Itoh, H., Mori, T., Masuzaki, H., Hosoda, K., Ogawa, Y., et al. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.9.5117 · Cited by 301
“Therefore, increased leptin secretion might contribute to increased sympathetic activity in PE. Moreover, intracerebroventricular or chronic (over 1 week) iv infusion of leptin increases arterial pressure in rats (34, 35), suggesting the possible involvement of elevated plasma leptin in the development of hypertension…”
BackgroundNicotinic receptor‐mediated effects on appetite and food intake
Jo, Y., Talmage, D. A., & Role, L. W. (2002) · Journal of Neurobiology · doi:10.1002/neu.10147 · Cited by 323
“Nicotine—like many other anorexigenic substances, including leptin, CCK, and insulin— generally exerts opposite effects on the regulation of sympathetic outflow and appetite (Haynes et al., 1997; Yettefti et al., 1997; Niijima, 1998; Krisufek et al., 1999; Sha and Szurszewski, 1999; Bray, 2000).”
BackgroundLevin, B. E., Dunn-Meynell, A. A., & Banks, W. A. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00393.2003 · Cited by 269
“Aside from its generally catabolic effect on energy homeostasis, leptin increases both general sympathetic activity and blood pressure (18, 26).”
BackgroundEnriori, P. J., Evans, A. E., Sinnayah, P., & Cowley, M. A. (2006) · Obesity · doi:10.1038/oby.2006.319 · Cited by 281
“Activation of central leptin receptors increases the activity of the sympathetic nervous system (17,18) which stimulates energy expenditure in adipose tissue (19–21).”
BackgroundEffects of Leptin on Insulin Sensitivity in Normal Rats
Sivitz, W. I., Walsh, S. A., Morgan, D. A., Thomas, M. J., & Haynes, W. G. (1997) · Endocrinology · doi:10.1210/endo.138.8.5327 · Cited by 268
“Third, we recently observed that leptin infusion to anesthetized rats increased brown adipose tissue sympathetic nerve activity measured by direct recording from nerves inervating interscapular fat ( 29 ).”
BackgroundSelf-citationIndependent Association Between Plasma Leptin and C-Reactive Protein in Healthy Humans
Shamsuzzaman, A., Winnicki, M., Wolk, R. A., Svatikova, A., Phillips, B. G., Davison, D. E., Berger, P. B., & Somers, V. K. (2004) · Circulation · doi:10.1161/01.cir.0000127960.28627.75 · Cited by 262
Mark, A. L., Shaffer, R. A., Correia, M. L. G., Morgan, D. A., Sigmund, C. D., & Haynes, W. G. (1999) · Journal of Hypertension · doi:10.1097/00004872-199917121-00026 · Cited by 254
Self-citationRegulation of leptin production: sympathetic nervous system interactions
Rayner, D. V., & Trayhurn, P. (2001) · Journal of Molecular Medicine · doi:10.1007/s001090100198 · Cited by 250
Lam, Q. L. K., & Lu, L. (2007) · PubMed · Cited by 247
Role of the melanocortin-4 receptor in metabolic rate and food intake in mice
Chen, A. S., Metzger, J. M., Trumbauer, M. E., Guan, X.-M., Yu, H., Frazier, E. G., Marsh, D. J., Forrest, M. J., Gopal-Truter, S., Fisher, J. K., et al. (2000) · Transgenic Research · doi:10.1023/a:1008983615045 · Cited by 247
“It is possible that decreased sympathetic activity, resulting from a loss of MC-4R signaling (Haynes et al., 1999), could be obscured by sympathetic activation of thermogenic organs via non MC-4R mediated pathways in response to increased adiposity ( Haynes et al., 1997 ).”
BackgroundObesity and adipokines: effects on sympathetic overactivity
Smith, M. M., & Minson, C. T. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.221036 · Cited by 245
Adiposity and Cardiovascular Disorders
Katagiri, H., Yamada, T., & Oka, Y. (2007) · Circulation Research · doi:10.1161/circresaha.107.151621 · Cited by 241
Plasma leptin and prognosis in patients with established coronary atherosclerosis
Wolk, R. A., Berger, P. B., Lennon, R. J., Brilakis, E. S., Johnson, B. D., & Somers, V. K. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.07.050 · Cited by 235
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
Leptin and its receptors: regulators of whole-body energy homeostasis
Houseknecht, K. L., & Portocarrero, C. P. (1998) · Domestic Animal Endocrinology · doi:10.1016/s0739-7240(98)00035-6 · Cited by 232
Manrique, C. M., Lastra, G., Gardner, M., & Sowers, J. R. (2009) · Medical Clinics of North America · doi:10.1016/j.mcna.2009.02.014 · Cited by 232
“Additionally leptin, which is elevated in obesity, increases sympathetic nerve activation.(12) The role of leptin in the control of sympathetic tone and blood pressure is supported by the observation that humans with leptin deficiency exhibit sympathetic system dysfunction and postural hypotension.”
BackgroundSympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications
Kalil, G. Z., & Haynes, W. G. (2011) · Hypertension Research · doi:10.1038/hr.2011.173 · Cited by 234
Self-citationSatoh, N., Ogawa, Y., Katsuura, G., Numata, Y., Tsuji, T., Hayase, M., Ebihara, K., Masuzaki, H., Hosoda, K., Yoshimasa, Y., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.9.1787 · Cited by 223
The Effect of Nutrition on Blood Pressure
Savica, V., Bellinghieri, G., & Kopple, J. D. (2010) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-010510-103954 · Cited by 231
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
Self-citationLeptin signaling in brain: A link between nutrition and cognition?
Morrison, C. D. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.12.004 · Cited by 229
“These observations were extended when it was clearly described that leptin increases energy expenditure and fat oxidation [47–49], at least in part via an activation of the sympathetic nervous system [50, 51], and a resultant activation of brown adipose tissue (BAT) [52–54], although leptin decreases body adiposity an…”
BackgroundInsulin Resistance the Hinge Between Hypertension and Type 2 Diabetes
Mancusi, C., Izzo, R., Gioia, G. D., Losi, M. A., Barbato, E., & Morisco, C. (2020) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-020-00408-8 · Cited by 232
Morrison, S. F., Sved, A. F., & Passerin, A. M. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.2.r290 · Cited by 217
“Although the hypothalamus plays a critical role in the initiation and control of a variety of processes that involve an increase in BAT metabolic activity, such as the thermogenic response to environmental cold (7), the febrile response to pathogens (10), and the energy expenditure in response to leptin (15) and other…”
BackgroundSelective 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
Self-citationEffects of Leptin on the Skeleton
Reid, I. R., Baldock, P. A., & Cornish, J. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00226 · Cited by 215
Role of leptin in blood pressure regulation and arterial hypertension
Bełtowski, J. (2006) · Journal of Hypertension · doi:10.1097/01.hjh.0000222743.06584.66 · Cited by 220
The glucoregulatory actions of leptin
D'souza, A. M., Neumann, U. H., Glavas, M. M., & Kieffer, T. J. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.04.011 · Cited by 220
Leptin-induced endothelial dysfunction in obesity
Korda, M., Kubant, R., Patton, S., & Malinski, T. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00479.2008 · Cited by 213
Leptin in Leanness and Obesity
Perakakis, N., Farr, O. M., & Mantzoros, C. S. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.11.069 · Cited by 230
Brown adipose tissue activity as a target for the treatment of obesity/insulin resistance
Poher, A.-L., Altirriba, J., Veyrat‐Durebex, C., & Rohner‐Jeanrenaud, F. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00004 · Cited by 219
“It is a well-known hormone increasing BAT activity and inducing “browning” of WAT via activation of the sympathetic nervous system and resulting increased β3 adrenoceptor signaling (Haynes et al., 1997; Commins et al., 2000).”
BackgroundKontogianni, M. D., Dafni, U. G., Routsias, J. G., & Skopouli, F. N. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040107 · Cited by 209
Metadata
- Authors
- Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I.
- Affiliations
- University of Iowa (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1997-07-15
- Volume
- 100
- Issue
- 2
- Pages
- 270-278
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC508189
- OpenAlex
- W2061340727
- Cited by
- 979
- References
- 29
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 17 · 2023: 11 · 2022: 14 · 2021: 17 · 2020: 15 · 2019: 13 · 2018: 11 · 2017: 31 · 2016: 29 · 2015: 25 · 2014: 44 · 2013: 34 · 2012: 43
- FWCI
- 14.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Wellcome Trust
- National Institutes of Health (5p50hl044546-05, 5r29hl043514-05)
- National Heart, Lung, and Blood Institute (HL-43514, HL-44546)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-25295, P30DK025295)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- leptin, sympathetic activity, brown adipose tissue, renal sympathetic nerve activity, adrenal gland, thermogenesis, leptin receptor, Zucker fatty rats, norepinephrine, energy homeostasis
- MeSH terms
- Action Potentials, Adrenal Glands, Animals, Blood Glucose, Adipose Tissue, Brown, Disease Models, Animal, Hemodynamics, Hindlimb, Insulin, Kidney, Male, Obesity, Proteins, Rats, Zucker, Sympathetic Nervous System, Rats, Sprague-Dawley, Leptin, Rats
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