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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 obesity, lipolytic capacity is suppressed through multiple mechanisms including impaired sympathetic nervous system signaling and reduced expression of lipolytic enzymes (Thorp and Schlaich 2015).”
Life’s Crucial 9 and NAFLD from association to SHAP-interpreted machine learning predictions
Xi, J., Chen, Y., Jie, C., Law, J. C. S., Fan, Z., & Lv, G. (2025) · Scientific Reports · doi:10.1038/s41598-025-92777-0 · Cited by 5
Saleh, V., Afroundeh, R., Siahkouhian, M., & Asadi, A. (2021) · DOAJ (DOAJ: Directory of Open Access Journals) · doi:10.22038/ijp.2020.50908.4042 · Cited by 4
Safety of surgical denervation of the common hepatic artery in insulin‐resistant dogs
Kraft, G., Scott, M. F., Allen, E. J., Edgerton, D. S., Farmer, B., Azamian, B. R., & Cherrington, A. D. (2021) · Physiological Reports · doi:10.14814/phy2.14805 · Cited by 4
“The hypothesis that the sympathetic nervous system is overactive in those with obesity, insulin- resistant states, and, in general, in the metabolic syndrome is not a novel idea (Lohmeier & Iliescu, 2013; Thorp & Schlaich, 2015).”
BackgroundPostural Tachycardia Syndrome and COVID-19: Focus on Ivabradine Therapy
DIXIT, K., & Frishman, W. H. (2022) · Cardiology in Review · doi:10.1097/crd.0000000000000503 · Cited by 4
“26 Chronic stimulation of the SNS increases the risk of developing metabolic syndrome.”
BackgroundNiu, C., Liu, N., Wen, G., & Santtila, P. O. (2023) · Sexuality and Disability · doi:10.1007/s11195-023-09808-9 · Cited by 4
Wang, C., Zhao, Y. W., Hong, Q., Lei, Y., Wang, S., Wang, W., Wei, W., Sun, C., & Han, T. (2023) · Environmental Research · doi:10.1016/j.envres.2023.118070 · Cited by 4
Rafieian, M., Farbu, E. H., Höper, A. C., Valtonen, R. I. P., Hyrkäs-Palmu, H., Perkiömäki, J. S., Crandall, C. G., Jaakkola, J. J. K., & Ikäheimo, T. M. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1558471 · Cited by 4
Hursh, B. E., Fazeli, M. S., Wang, S., Marchant, E. A., Woo, P., Elango, R., Lavoie, P. M., Chanoine, J., & Collet, J. (2016) · Hormone Research in Paediatrics · doi:10.1159/000445685 · Cited by 4
Saiz-Satjes, M., & Martínez-Martín, F. J. (2018) · Drugs in Context · doi:10.7573/dic.212509 · Cited by 4
“Chronic hyperactivity of the sympathetic nervous system has been shown to promote the development of obesity, hyperglycemia, insulin resistance and hypertension [11,17,18,65].”
BackgroundAssociation between Sympathetic Nervous System Activation, Obesity and Insulin Resistance
Кочетков, А. И., Ostroumova, O. D., Starodubova, A. V., Оstroumova, Т. М., & Bondarenko, D. A. (2019) · Rational Pharmacotherapy in Cardiology · doi:10.20996/1819-6446-2019-15-2-230-243 · Cited by 4
Nazari, S., & Moosavi, S. M. S. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1739713 · Cited by 5
“…prevalence of the metabolic syndrome, which is a cluster of metabolic risk factors including atherogenic dyslipidemia, insulin resistance, obesity and hypertension that directly increase the risk of cardiovascular diseases and type-2 diabetes mellitus (Canale et al. 2013, Thorp and Schlaich 2015).”
BackgroundСергеевна, И. В., Ushakov, A., & Анатольевна, Г. А. (2022) · Current Cardiology Reviews · doi:10.2174/1573403x18666220617121144 · Cited by 4
“There is strong evidence suggesting that insulin resistance and hyperinsulinemia associated with T2DM cause sympathoexcitatory effect via direct action on hypothalamic nuclei in the central nervous system [15].”
BackgroundHuang, Y., Chen, H., Hu, D., & Wan, R. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.921287 · Cited by 4
Transcriptome analysis of norepinephrine-induced lipolysis in differentiated adipocytes of Bama pig
Li, H., Li, H., Zhang, J., Zhang, J., Zhang, G., Tong, X., Zhang, T., Wu, Y., Li, M., & Jin, L. G. (2023) · Gene · doi:10.1016/j.gene.2023.147753 · Cited by 4
Morcos, J. A., Ebeid, A. M., Khodeir, S. A., & El-Azab, G. A. (2017) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000759 · Cited by 3
“Diabetic patients have impaired responses to sympathetic signals to liver, pancreas, skeletal muscle, adrenal medulla and adipose tissue and show elevations in hepatic glucose production, insulin resistance and impaired pancreatic β-cell function [16].”
BackgroundMetabolic syndrome: what changed during last 30 years?
Татарчук, Т. Ф., Tutchenko, T. М., Perekhrestenko, O. V., Калашніков, О. О., & Glamazda, M. (2018) · Reproductive Endocrinology · doi:10.18370/2309-4117.2018.43.15-27 · Cited by 4
Does insulin signalling decide glucose levels in the fasting steady state?Preprint
Diwekar-Joshi, M., & Watve, M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/553016 · Cited by 4
Tian, A., Zheng, Y., Jin, J., & Huang, C.-Y. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1586530 · Cited by 3
“High-sugar and high-fat diets can also activate the sympathetic nervous system (35–37), resulting in increased blood pressure at night (38) and disturbed sleep architecture (39, 40).”
Cigaina, V., Saggioro, A., Fabris, P., Canaglia, A., Scalabrin, U., Cigaina, S., Wang, Q., Bonitta, G., & Bonavina, L. (2025) · Journal of Laparoendoscopic & Advanced Surgical Techniques · doi:10.1089/lap.2025.0093 · Cited by 3
Animal models of polycystic ovary syndrome
Kulkarni, S., Dahake, D., Gupta, K., Rathod, K., Aswar, U. M., & Thareja, S. (2025) · Systems Biology in Reproductive Medicine · doi:10.1080/19396368.2025.2551005 · Cited by 3
“The findings of the study indicate that NGF may directly contribute to hyperandrogenism and hyperinsulinemia (Thorp and Schlaich 2015).”
Zou, S., Lu, Y., & Tang, Y. (2025) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2025195 · Cited by 3
da Silva, T. M., Lima, W. G., Marques‐Oliveira, G. H., Dias, D. P. M., Granjeiro, É. M., Silva, L. E. V., Fazan, R., & Chaves, V. E. (2020) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2020.02.007 · Cited by 3
Protective Potential of Sodium-Glucose Cotransporter 2 Inhibitors in Internal Medicine (Part 2)
Арманович, А. А., Sheibani, M., Трофименко, А. И., Lysov, E. E., Khamidova, F. M., Aznauryan, A., Sukiasyan, L. M., Sahakyan, K., Gevorgyan, T. R., Tatoyan, M. R., et al. (2025) · Innovative medicine of Kuban · doi:10.35401/2541-9897-2025-10-1-101-109 · Cited by 3
Rabin, M., & Willard, C. L. (2020) · Springer eBooks · doi:10.1007/978-3-030-47668-7_16 · Cited by 3
Lucini, D., Malacarne, M., Pagani, M., Morizzo, C., Kozàkovà, M., Nannipieri, M., & Palombo, C. (2021) · Acta Diabetologica · doi:10.1007/s00592-020-01645-y · Cited by 3
Ishizu, L. Y., Borghi, F., Conceição-Vertamatti, A. G., Costa, G., Ramos, L., Áreas, M. A., & Kassisse, D. M. G. (2021) · Endocrine and Metabolic Science · doi:10.1016/j.endmts.2021.100112 · Cited by 4
“This result may be triggered by fasting, potentiating the lipolytic effects of high concentrations of catecholamines, corticosterone and ACTH (Chaves, et al., 2011, Thorp and Schlaich, 2015, Vendrame, et al., 2016, Wang, Gray, Kuo and Harris, 2012).”
BackgroundDas‐Earl, P., Schreihofer, D. A., Sumien, N., & Schreihofer, A. M. (2024) · Journal of Neurophysiology · doi:10.1152/jn.00409.2023 · Cited by 3
Golmohammadi, M., Attari, V. E., Salimi, Y., Nachvak, S. M., & Samadi, M. (2024) · Trials · doi:10.1186/s13063-024-08486-y · Cited by 3
Metabolic targets in the Postural Orthostatic Tachycardia Syndrome: A short thematic review
Glasgow, A. C., & Kim, J. Y. (2024) · Autonomic Neuroscience · doi:10.1016/j.autneu.2024.103232 · Cited by 3
Serhiyenko, V. A., Долинай, М., Sehin, V. B., Lazur, Y. V., & Serhiyenko, A. A. (2025) · INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine) · doi:10.22141/2224-0721.20.8.2024.1461 · Cited by 3
Dopaminergic Effects on Brown Adipose Tissue (DEBAT): A prospective physiological study
Bahler, L., Verberne, H. J., Soeters, M. R., Booij, J., Hoekstra, J. B. L., & Holleman, F. (2016) · Diabetes & Metabolism · doi:10.1016/j.diabet.2016.06.003 · Cited by 3
Correlation between body fat and post-exercise heart rate in healthy men and women
Jezdimirović, T., Semeredi, S., Štajer, V., Calleja-González, J., & Ostojić, S. M. (2017) · Science & Sports · doi:10.1016/j.scispo.2017.05.001 · Cited by 3
Carotid Bodies: Use of Chemosensitivity as a Biomarker in Prediabetes
Conde, S. V., Lages, M., Guarino, M. P., & Sacramento, J. F. (2022) · Biomarkers in disease · doi:10.1007/978-3-031-08014-2_38 · Cited by 3
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
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