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Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome
Open accessAbstract
Sympathetic tone is well recognised as being implicit in cardiovascular control. It is less readily acknowledged that activation of the sympathetic nervous system is integral in energy homeostasis and can exert profound metabolic effects. Accumulating data from animal and human studies suggest that central sympathetic overactivity plays a pivotal role in the aetiology and complications of several metabolic conditions that can cluster to form the Metabolic Syndrome (MetS). Given the known augmented risk for type 2 diabetes, cardiovascular disease, and premature mortality associated with the MetS understanding the complex pathways underlying the metabolic derangements involved has become a priority. Many factors have been proposed to contribute to increased sympathetic nerve activity in metabolic abnormalities including obesity, impaired baroreflex sensitivity, hyperinsulinemia, and elevated adipokine levels. Furthermore there is mounting evidence to suggest that chronic sympathetic overactivity can potentiate two of the key metabolic alterations of the MetS, central obesity and insulin resistance. This review will discuss the regulatory role of the sympathetic nervous system in metabolic control and the proposed pathophysiology linking sympathetic overactivity to metabolic abnormalities. Pharmacological and device-based approaches that target central sympathetic drive will also be discussed as possible therapeutic options to improve metabolic control in at-risk patient cohorts.
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“The SNS increases in response to caloric surplus, with norepinephrine activating β-adrenergic receptors, particularly in BAT. This stimulates UCP1 in BAT mitochondria, generating heat through uncoupled respiration.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [39]
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“In an elegant study by Straznicky et al., middle-aged subjects with the MetS who lost 9% of their body weight after undergoing a 12-week hypocaloric diet were shown to have significantly improved resting muscle sympathetic nerve activity, whole-body noradrenaline spillover, and whole-body insulin…”
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Chazova, I. E., & Schlaich, M. P. (2013) · International Journal of Hypertension · doi:10.1155/2013/541689 · Cited by 60 · cited 1×
“6mmol/L in triglycerides, and decline of 5 beats/minute in heart rate [93].”
BackgroundSelf-citationConsequences of the Increased Autonomic Nervous Drive in Hypertension, Heart Failure and Diabetes
Julius, M. (1998) · Blood Pressure · doi:10.1080/080370598438410-1 · Cited by 55
Central sympatholytic therapy has anti-inflammatory properties in hypertensive postmenopausal women
Pöyhönen‐Alho, M., Manhem, K., Katzman, P., Kibarskis, A., Antikaínen, R., Erkkola, R. U., Tuomilehto, J. O., Ebeling, P. E., & Kaaja, R. (2008) · Journal of Hypertension · doi:10.1097/hjh.0b013e328311cf37 · Cited by 51
The Functional Importance of Sympathetic Nerves to the Liver and Endocrine Pancreas
Järhult, J., FALCK, B., Ingemansson, S., & Nobin, A. (1979) · Annals of Surgery · doi:10.1097/00000658-197901000-00018 · Cited by 51
Straznicky, N. E., Lambert, G. W., McGrane, M. T., Masuo, K., Dawood, T., Nestel, P. J., Eikelis, N., Schlaich, M. P., Esler, M., Socratous, F., et al. (2009) · Diabetes · doi:10.2337/db08-1595 · Cited by 51
Self-citationKrespi, P. G., Makris, T. K., Hatzizacharias, A. N., Triposkiadis, P., Tsoukala, C., Kyriaki, D., Votteas, V., & Kyriakidis, M. (1998) · Cardiovascular Drugs and Therapy · doi:10.1023/a:1007702132210 · Cited by 43
Metabolic Syndrome and Hyperglycemia: Congruence and Divergence
Alexander, C. M., Landsman, P. B., & Grundy, S. M. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.04.046 · Cited by 43 · cited 1×
“…that govern the sympathetic nervous system are yet to be fully elucidated, sympathetic tone is recognised as an important mediator of cardiovascular function predominantly through its direct effects on beta-adrenergic receptors in the heart to modulate cardiac output and on alpha-adrenergic…”
BackgroundThe Effect of Moxonidine on Endothelial Dysfunction in Metabolic Syndrome
Topal, E., Çıkım, A. S., Çıkım, K., Temel, İ., & Оздемир, Р. (2006) · American Journal of Cardiovascular Drugs · doi:10.2165/00129784-200606050-00007 · Cited by 40
Lithell, H., Pollare, T., Berne, C., & Saltin, B. (1992) · Blood Pressure · doi:10.3109/08037059209065120 · Cited by 31
Sympathetic and haemodynamic responses to lipids in healthy human ageing
Florian, J. P., & Pawelczyk, J. A. (2010) · Experimental Physiology · doi:10.1113/expphysiol.2009.050997 · Cited by 23
Ciriello, J. (2013) · Peptides · doi:10.1016/j.peptides.2013.03.021 · Cited by 19 · cited 1×
“…study by Straznicky et al., middle-aged subjects with the MetS who lost 9% of their body weight after undergoing a 12-week hypocaloric diet were shown to have significantly improved resting muscle sympathetic nerve activity, whole-body noradrenaline spillover, and whole-body insulin sensitivity.”
BackgroundRenal norepinephrine spillover during infusion of nonesterified fatty acids
Grekin, R. J., Ngarmukos, C., Williams, D. M., & Supiano, M. A. (2005) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2004.10.013 · Cited by 14 · cited 1×
“Latest findings from pharmaceutical and device-based clinical trials are encouraging for targeting central sympathetic activity to improve metabolic control in patients with the MetS who are at heightened risk for diabetes and cardiovascular disease.”
BackgroundVettor, R., Zarjevski, N., Cusin, I., et al. (1994) · Diabetologia · doi:10.1007/s001250050236 · Cited by 13
Lipolytic sensitivity and response to fasting in normotensive and hypertensive obese humans
Townsend, R. R., & Klein, S. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90282-1 · Cited by 8 · cited 1×
“Evidence in support of weight gain being directly related to decreased beta-adrenergic responsiveness comes from studies that show that both short-term [77] and chronic [78, 79] pharmacological blockade of beta-receptors leads to an increase in body weight.”
BackgroundMatsuzawa, Y. (1997) · doi:10.1002/(sici)1099-0895(199703)13:1
Flagged first, then by citations
Research works printed but not linked: 7
- 1986, Quarterly Journal of Medicine, 61, 1081
- 1995, The American Journal of Physiology, 269, R222
- 10.1210/en.133.4.1753 · DOI
- 1992, The Journal of Clinical Investigation, 90, 27
- 2008, Jounral of Hypertension, 26, S347
- 1998, Blood Pressure, Supplement, 7, 5
- 2010, Arterial Hypertension (Greek), 19, 32
Cited by
Sorted by citations
Heart rate variability in type 2 diabetes mellitus: A systematic review and meta–analysis
Benichou, T., Pereira, B., Mermillod, M., Tauveron, I., Pfabigan, D., Maqdasy, S., & Dutheil, F. (2018) · PLOS ONE · doi:10.1371/journal.pone.0195166 · Cited by 419
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
Heart Failure With Preserved Ejection Fraction and Diabetes
McHugh, K., DeVore, A. D., Wu, J., Matsouaka, R. A., Fonarow, G. C., Heidenreich, P. A., Yancy, C. W., Green, J. B., Altman, N., & Hernandez, A. F. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.033 · Cited by 313
SGLT2 Inhibitor–Induced Sympathoinhibition
Herat, L. Y., Magno, A. L., Rudnicka, C., Hricova, J., Carnagarin, R., Ward, N. C., Arcambal, A., Kiuchi, M. G., Head, G. A., Schlaich, M. P., et al. (2020) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2019.11.007 · Cited by 233
“There is clear evidence to indicate that obesity, metabolic syndrome, and type 2 diabetes are associated with chronic activation of sympathetic nervous tone (7,8).”
BackgroundSelf-citationRole of the sympathetic nervous system in regulation of the sodium glucose cotransporter 2
Matthews, V. B., Elliot, R. H., Rudnicka, C., Hricova, J., Herat, L., & Schlaich, M. P. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001434 · Cited by 222
“Sympathetic activity is upregulated in obesity and type 2 diabetes and associated with perturbed glucose homeostasis, as recently reviewed in detail [5,6].”
BackgroundInfluentialSelf-citation
Metadata
- Authors
- Thorp, A. A., & Schlaich, M. P.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Corresponding author
- Schlaich, Markus P.
- ORCID
- Schlaich, Markus P.
- Venue
- Journal of Diabetes Research
- Publisher
- Wiley
- Published
- 2015
- Volume
- 2015
- Pages
- 1-11
- ISSN
- 2314-6745 (ISSN-L)
- 2314-6753
- PMC
- PMC4430650
- OpenAlex
- W2066041574
- Cited by
- 425
- References
- 101
- Citations by year
- 2026: 28 · 2025: 42 · 2024: 36 · 2023: 44 · 2022: 40 · 2021: 45 · 2020: 48 · 2019: 40 · 2018: 33 · 2017: 31 · 2016: 32 · 2015: 5
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Diabetes Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Health and Medical Research Council
- Victorian Government’s Operational Infrastructure Support Program
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- sympathetic nervous system, sympathetic hyperactivity, obesity, metabolic syndrome, energy homeostasis, abdominal obesity, insulin resistance, baroreflex sensitivity, hyperinsulinemia, adipokines, type 2 diabetes, cardiovascular disease, sympathetic activity, device therapy
- MeSH terms
- Animals, Humans, Obesity, Sympathetic Nervous System, Metabolic Syndrome
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.
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